HIV-1感染者Vpr基因多态性及其临床意义研究
|
摘要
[目的]
探讨HIV-1感染者亚型的分子流行病学特征和HIV-1Vpr基因的多态性及其临床意义。
[方法]
研究对象来自我国“十一五”HIV/AIDS抗病毒治疗队列一(即初治患者)。提取323例HIV-1感染者血浆HIV-RNA,采用RT-PCR的方法对Vpr基因进行扩增、测序。利用Contig Express软件、Bioedit5.0软件、美国拉莫斯国家实验室Los Alamos网站上的HIV databases, ClustalW软件、Mega4.1软件,构建系统进化树、鉴定病毒亚型并与Env/Gag基因分型结果进行比较、比对氨基酸序列。收集患者在基线和治疗48周时的临床数据信息(包括性别、年龄、传播途径、CD4+T淋巴细胞计数、HIV病毒载量、血肌酐、肾小球滤过率eGFR>肌酐清除率Ccr)。分析我国HIV-1感染者亚型的分子流行病学特征和HIV-1Vpr基因的多态性及其临床意义。
[结果]
1.我国HIV-1感染者亚型的分子流行病学特征
我国HIV-1感染者以男性为主占74.7%,年龄18-49岁的感染者占87.0%,主要流行株为CRF01_AE亚型占46%,同时有BC亚型(28%)(包括CRF07_BC亚型(19%)、CRF08_BC(9%))、B亚型(23%)、CRF03_AB亚型(2%)及C亚型(1%),其中CRF01_AE亚型主要分布在北京、上海、广州,BC亚型主要分布在云南,B亚型主要分布在河南。本研究中,性途径为主要传播途径占83.0%,其中异性传播占43.0%,同性传播占38.3%,异性传播：同性传播大致1：1。同性传播以CRF01_AE亚型为主,血液传播以B亚型为主。合并HBV感染的共感染率是15.0%。采用HIV-1Vpr基因对我国HIV-1毒株进行分型与Env/Gag基因分型结果一致性高达95.3%,且操作简单、方便,经济。
2.不同HIV-1亚型对抗病毒治疗临床疗效的影响
在治疗基线时,CRF01_AE亚型感染者的CD4+T淋巴细胞计数显著低于其它亚型(P=0.007)。治疗48周时CRF01_AE、CRF07_BC、CRF08_BC、B亚型感染者均出现CD4+T淋巴细胞计数升高、血浆HIV-1病毒载量显著下降,但不同HIV-1亚型抗病毒治疗临床疗效间无显著差异。
3.我国HIV-1感染者Vpr基因的多态性及其临床意义
我国HIV/AIDS初治患者HIV-1Vpr基因氨基酸保守位点所占比例为41.7%,变异位点较为分散,C末端变异较N末端明显。我国HIV-1感染者Vpr氨基酸序列第77位为谷氨酰胺(Q)的比例高达81.7%,与国外研究报道的该位点多为精氨酸(R)不同。我国HIV-1感染者Vpr氨基酸序列R85P和Q86G变异者基线CD4+T淋巴细胞计数显著低于未变异者而血浆HIV-1病毒载量显著高于未变异者(均P<0.05)；A89G变异者基线及治疗48周时CD4+T淋巴细胞计数显著低于未变异者(均P<0.05)；184L变异者基线血浆HIV-1病毒载量显著低于未变异者,治疗48周时CD4+T淋巴细胞计数显著高于未变异者(均P<0.05)；E55A变异者基线CD4+T淋巴细胞计数显著高于未变异者(P=0.038)。
[结论]
该研究提出使用HIV-1Vpr基因进行我国HIV-1毒株基因亚型分析准确度高、方便、经济。我国HIV-1感染者以男性为主,CRF01_AE亚型为主要流行株,性途径为主要传播途径,同性与异性传播比例大致相当。CRF01_AE亚型感染者疾病进展快,不同HIV-1亚型对抗病毒治疗临床疗效无影响。我国HIV-1感染者Vpr基因R77Q氨基酸位点变异频率远高于国外报道,R85P、Q86G、A89G和E55A变异可能与疾病进程有关。该研究不仅揭示了我国HIV-1感染者亚型的分子流行病学特征和HIV-1Vpr基因的多态性及其临床意义,而且对于指导我国HIV-1感染者的疾病监控、指导疫苗研发、提供潜在的治疗干预手段都有着重要意义。
[Objective]
To discuss the molecular epidemiologcal characteristic of HIV-1subtypes and HIV-1Vpr gene diversity and its Clinical significances among Chinese HIV-1infected patients.
[Methods]
The patients were screened from antiretroviral therapy cohort of the national11th Five-year Plan in Chinese treatment-naive HIV/AIDS patients. We assessed the different influencing factors of AIDS disease progression (including gender, age, ethnicity, sexual transmission mode, the baseline CD4+T lymphocyte count, baseline HIV viral load). HIV RNA were extracted from plasma samples of total323patients, and the Vpr gene were amplified by RT-PCR and nested-PCR. Using Contig Express software, Bioedit5.0software, the United States Alamos National Laboratory Los Alamos site HIV databases, Clustal W software, Mega4.1software, we constructed the phylogenetic trees to confirm the virus subtype. We compared the two results of virus subtype which were genotyped by vpr gene and env/gag gene, analyzed the deduced amino acid sequence. We collected and calculated the clinical data at baseline and the end of48weeks' combined antiretroviral therapy (including gender, age, transmission mode, CD4+T lymphocyte count, HIV viral load, serum creatinine, estimated glomerular filtration rate (eGFR) and clearance of creatinine). We described the molecular epidemiologcal characteristic of HIV-1subtypes and identified the characteristics of the polymorphism of HIV-1Vpr gene and its clinical significances among Chinese HIV-1infected patients.
[Results]
1. The molecular epidemiologcal characteristic of HIV-1subtypes among Chinese HIV-1infected patients
Most of the Chinese HIV-1infected patients are male accounted for74.7%. Patients with age18to49years old accounted for87.0%. The majority subtype was CRF01_AE accounted for46%. There were other subtypes including subtype BC(28%)(CRF07_BC(19%), CRF08_BC(9%))、subtype B(23%)、subtype CRF03_AB(2%) and subtype C(1%). The subtype CRF01_AE was mainly distributed in Beijing, Shanghai, and Guangzhou. Subtype BC (CRF07_BC、CRF08_BC) were mainly distributed in Yunnan. Subtype B was mainly distributed in Henan. Sexually-transmitted population accounts for83.0%Chinese HIV-1infected patients, which included43.0%homosexual transmitted patients and38.3%heterosexual transmitted patients. The ratio is roughly1:1between homosexual and heterosexual transmission patterns. The spread of subtype CRF01_AE is mainly through homosexual transmission. Subtype B predominates in patients through Blood transmission. The co-infection prevalence of HIV-1and HBV is15.0%and of HIV-1and HCV is11.3%among Chinese HIV-1infected patients. The co-infection prevalence of HIV-1and HCV was much higher in patients infected with subtype B (26.5%) than others (P=0.000). Comparing the methods for identifying the subtypes of HIV-1when HIV-1env/gag gene was used to analyze, the consistence of results is up to94%, and it is an accurate, simple, convenient and cost savings method when HIV-1Vpr gene was used to analyze.
2. The impact of different HIV-1subtypes on clinical effect of antiretroviral treatment
At baseline, patients infected with subtype CRF01_AE have a lower CD4+T lymphocyte count than others (P=0.007). At the end of48weeks, the results that the CD4+T lymphocyte count increased and plasma HIV-1viral load significantly decreased, were found among patients infected with subtype CRF01_AE, subtype CRF07_BC, CRF08_BC and subtype B, but there were no significant difference according to HIV-1subtype in the clinical effect of antiretroviral treatment.
3. HIV-1Vpr gene diversity and its Clinical significances among Chinese HIV-1infected patients
The conservative sites of HIV-1Vpr took41.7%in the whole deduced amino acid residues among Chinese HIV-1infected patients. The mutation sites distributed more dispersed. The occurrence of viriation in the C-term was more obvious than that in the N-term. In the77th position,81.7%of the300amino acid sequences were glutamine (Q), which differ from overseas reports most of them were Arginine (R). Among Chinese HIV-1infected patients, Vpr R85P and Q86G have been associated with a lower CD4+T lymphocyte count and a higher plasma HIV-1viral load at baseline (P<0.05). Vpr A89G has been associated with a lower CD4+T lymphocyte count at baseline and at the end of48weeks (P<0.05). Vpr I84L has been associated with a lower plasma HIV-1viral load at baseline and a higher CD4+T lymphocyte count at the end of48weeks (P<0.05). Vpr E55A has been associated with a higher CD4+T lymphocyte count at baseline (P=0.038)。
[Conclusions]
This study proposed that it is convenient and feasible we when use phylogenetic trees of Vpr gene to confirm the HIV-1subtypes among Chinese HIV-1infected patients. The majority of Chinese HIV-1infected patients are male. CRF01_AE is a predominant HIV-1subtype in Chinese HIV-1infected patients. Sexual transmission is the main route of transmission. The ratio is roughly equal between homosexual and heterosexual transmission patterns. Patients infected with CRF01_AE are associated with fast progression to AIDS. This study finds no significant difference in the clinical effect of antiretroviral treatment among patients infected with different HIV-1subtypes. Among Chinese HIV-1infected patients, the mutation frequency of Vpr R77Q is higher than overseas reports. Vpr R85P and Q86G, A89G may be associated with a fast progression to AIDS. However, Vpr E55A may be associated with a slow progression to AIDS.This study not only revealed the molecular epidemiologcal characteristic of HIV-1subtypes and HIV-1Vpr gene diversity and its clinical significances among Chinese HIV-1infected patients, but also could guide the disease surveillance, assist the HIV-1vaccine development and provide potential treatments.
探讨HIV-1感染者亚型的分子流行病学特征和HIV-1Vpr基因的多态性及其临床意义。
[方法]
研究对象来自我国“十一五”HIV/AIDS抗病毒治疗队列一(即初治患者)。提取323例HIV-1感染者血浆HIV-RNA,采用RT-PCR的方法对Vpr基因进行扩增、测序。利用Contig Express软件、Bioedit5.0软件、美国拉莫斯国家实验室Los Alamos网站上的HIV databases, ClustalW软件、Mega4.1软件,构建系统进化树、鉴定病毒亚型并与Env/Gag基因分型结果进行比较、比对氨基酸序列。收集患者在基线和治疗48周时的临床数据信息(包括性别、年龄、传播途径、CD4+T淋巴细胞计数、HIV病毒载量、血肌酐、肾小球滤过率eGFR>肌酐清除率Ccr)。分析我国HIV-1感染者亚型的分子流行病学特征和HIV-1Vpr基因的多态性及其临床意义。
[结果]
1.我国HIV-1感染者亚型的分子流行病学特征
我国HIV-1感染者以男性为主占74.7%,年龄18-49岁的感染者占87.0%,主要流行株为CRF01_AE亚型占46%,同时有BC亚型(28%)(包括CRF07_BC亚型(19%)、CRF08_BC(9%))、B亚型(23%)、CRF03_AB亚型(2%)及C亚型(1%),其中CRF01_AE亚型主要分布在北京、上海、广州,BC亚型主要分布在云南,B亚型主要分布在河南。本研究中,性途径为主要传播途径占83.0%,其中异性传播占43.0%,同性传播占38.3%,异性传播：同性传播大致1：1。同性传播以CRF01_AE亚型为主,血液传播以B亚型为主。合并HBV感染的共感染率是15.0%。采用HIV-1Vpr基因对我国HIV-1毒株进行分型与Env/Gag基因分型结果一致性高达95.3%,且操作简单、方便,经济。
2.不同HIV-1亚型对抗病毒治疗临床疗效的影响
在治疗基线时,CRF01_AE亚型感染者的CD4+T淋巴细胞计数显著低于其它亚型(P=0.007)。治疗48周时CRF01_AE、CRF07_BC、CRF08_BC、B亚型感染者均出现CD4+T淋巴细胞计数升高、血浆HIV-1病毒载量显著下降,但不同HIV-1亚型抗病毒治疗临床疗效间无显著差异。
3.我国HIV-1感染者Vpr基因的多态性及其临床意义
我国HIV/AIDS初治患者HIV-1Vpr基因氨基酸保守位点所占比例为41.7%,变异位点较为分散,C末端变异较N末端明显。我国HIV-1感染者Vpr氨基酸序列第77位为谷氨酰胺(Q)的比例高达81.7%,与国外研究报道的该位点多为精氨酸(R)不同。我国HIV-1感染者Vpr氨基酸序列R85P和Q86G变异者基线CD4+T淋巴细胞计数显著低于未变异者而血浆HIV-1病毒载量显著高于未变异者(均P<0.05)；A89G变异者基线及治疗48周时CD4+T淋巴细胞计数显著低于未变异者(均P<0.05)；184L变异者基线血浆HIV-1病毒载量显著低于未变异者,治疗48周时CD4+T淋巴细胞计数显著高于未变异者(均P<0.05)；E55A变异者基线CD4+T淋巴细胞计数显著高于未变异者(P=0.038)。
[结论]
该研究提出使用HIV-1Vpr基因进行我国HIV-1毒株基因亚型分析准确度高、方便、经济。我国HIV-1感染者以男性为主,CRF01_AE亚型为主要流行株,性途径为主要传播途径,同性与异性传播比例大致相当。CRF01_AE亚型感染者疾病进展快,不同HIV-1亚型对抗病毒治疗临床疗效无影响。我国HIV-1感染者Vpr基因R77Q氨基酸位点变异频率远高于国外报道,R85P、Q86G、A89G和E55A变异可能与疾病进程有关。该研究不仅揭示了我国HIV-1感染者亚型的分子流行病学特征和HIV-1Vpr基因的多态性及其临床意义,而且对于指导我国HIV-1感染者的疾病监控、指导疫苗研发、提供潜在的治疗干预手段都有着重要意义。
[Objective]
To discuss the molecular epidemiologcal characteristic of HIV-1subtypes and HIV-1Vpr gene diversity and its Clinical significances among Chinese HIV-1infected patients.
[Methods]
The patients were screened from antiretroviral therapy cohort of the national11th Five-year Plan in Chinese treatment-naive HIV/AIDS patients. We assessed the different influencing factors of AIDS disease progression (including gender, age, ethnicity, sexual transmission mode, the baseline CD4+T lymphocyte count, baseline HIV viral load). HIV RNA were extracted from plasma samples of total323patients, and the Vpr gene were amplified by RT-PCR and nested-PCR. Using Contig Express software, Bioedit5.0software, the United States Alamos National Laboratory Los Alamos site HIV databases, Clustal W software, Mega4.1software, we constructed the phylogenetic trees to confirm the virus subtype. We compared the two results of virus subtype which were genotyped by vpr gene and env/gag gene, analyzed the deduced amino acid sequence. We collected and calculated the clinical data at baseline and the end of48weeks' combined antiretroviral therapy (including gender, age, transmission mode, CD4+T lymphocyte count, HIV viral load, serum creatinine, estimated glomerular filtration rate (eGFR) and clearance of creatinine). We described the molecular epidemiologcal characteristic of HIV-1subtypes and identified the characteristics of the polymorphism of HIV-1Vpr gene and its clinical significances among Chinese HIV-1infected patients.
[Results]
1. The molecular epidemiologcal characteristic of HIV-1subtypes among Chinese HIV-1infected patients
Most of the Chinese HIV-1infected patients are male accounted for74.7%. Patients with age18to49years old accounted for87.0%. The majority subtype was CRF01_AE accounted for46%. There were other subtypes including subtype BC(28%)(CRF07_BC(19%), CRF08_BC(9%))、subtype B(23%)、subtype CRF03_AB(2%) and subtype C(1%). The subtype CRF01_AE was mainly distributed in Beijing, Shanghai, and Guangzhou. Subtype BC (CRF07_BC、CRF08_BC) were mainly distributed in Yunnan. Subtype B was mainly distributed in Henan. Sexually-transmitted population accounts for83.0%Chinese HIV-1infected patients, which included43.0%homosexual transmitted patients and38.3%heterosexual transmitted patients. The ratio is roughly1:1between homosexual and heterosexual transmission patterns. The spread of subtype CRF01_AE is mainly through homosexual transmission. Subtype B predominates in patients through Blood transmission. The co-infection prevalence of HIV-1and HBV is15.0%and of HIV-1and HCV is11.3%among Chinese HIV-1infected patients. The co-infection prevalence of HIV-1and HCV was much higher in patients infected with subtype B (26.5%) than others (P=0.000). Comparing the methods for identifying the subtypes of HIV-1when HIV-1env/gag gene was used to analyze, the consistence of results is up to94%, and it is an accurate, simple, convenient and cost savings method when HIV-1Vpr gene was used to analyze.
2. The impact of different HIV-1subtypes on clinical effect of antiretroviral treatment
At baseline, patients infected with subtype CRF01_AE have a lower CD4+T lymphocyte count than others (P=0.007). At the end of48weeks, the results that the CD4+T lymphocyte count increased and plasma HIV-1viral load significantly decreased, were found among patients infected with subtype CRF01_AE, subtype CRF07_BC, CRF08_BC and subtype B, but there were no significant difference according to HIV-1subtype in the clinical effect of antiretroviral treatment.
3. HIV-1Vpr gene diversity and its Clinical significances among Chinese HIV-1infected patients
The conservative sites of HIV-1Vpr took41.7%in the whole deduced amino acid residues among Chinese HIV-1infected patients. The mutation sites distributed more dispersed. The occurrence of viriation in the C-term was more obvious than that in the N-term. In the77th position,81.7%of the300amino acid sequences were glutamine (Q), which differ from overseas reports most of them were Arginine (R). Among Chinese HIV-1infected patients, Vpr R85P and Q86G have been associated with a lower CD4+T lymphocyte count and a higher plasma HIV-1viral load at baseline (P<0.05). Vpr A89G has been associated with a lower CD4+T lymphocyte count at baseline and at the end of48weeks (P<0.05). Vpr I84L has been associated with a lower plasma HIV-1viral load at baseline and a higher CD4+T lymphocyte count at the end of48weeks (P<0.05). Vpr E55A has been associated with a higher CD4+T lymphocyte count at baseline (P=0.038)。
[Conclusions]
This study proposed that it is convenient and feasible we when use phylogenetic trees of Vpr gene to confirm the HIV-1subtypes among Chinese HIV-1infected patients. The majority of Chinese HIV-1infected patients are male. CRF01_AE is a predominant HIV-1subtype in Chinese HIV-1infected patients. Sexual transmission is the main route of transmission. The ratio is roughly equal between homosexual and heterosexual transmission patterns. Patients infected with CRF01_AE are associated with fast progression to AIDS. This study finds no significant difference in the clinical effect of antiretroviral treatment among patients infected with different HIV-1subtypes. Among Chinese HIV-1infected patients, the mutation frequency of Vpr R77Q is higher than overseas reports. Vpr R85P and Q86G, A89G may be associated with a fast progression to AIDS. However, Vpr E55A may be associated with a slow progression to AIDS.This study not only revealed the molecular epidemiologcal characteristic of HIV-1subtypes and HIV-1Vpr gene diversity and its clinical significances among Chinese HIV-1infected patients, but also could guide the disease surveillance, assist the HIV-1vaccine development and provide potential treatments.
引文
[1]Coffin J, Haase A, Levy J A, et al. Human immunodeficiency viruses [J]. Science, 1986,232(4751):697.
[2]Center for Disease Control (CDC). Pneumocystis pneumonia Los Angeles [J]. MMWR Morb Mortal Wkly Rep,1981,30(21):250-252.
[3]Pincock S. Francoise Barre-Sinoussi:shares Nobel Prize for discovery of HIV [J]. Lancet,2008,372(9647):1377.
[4]临床病理讨论.第96例—发热、咳嗽、进行性呼吸困难[J].中华内科杂志,1986,25(7)：436-439.
[5]UNAIDS. Report on the global AIDS epidemic 2012. Geneva:UNAIDS, 2012;http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/ 2012/gr2012/20121120_UNAIDS_Global_Report_2012_with_annexes_en.pdf
[6]中华人民共和国卫生部,联合国艾滋病规划署,世界卫生组织.2011年中国艾滋病疫情评估[J].中国艾滋病性病,2011,18(1)：1-5.
[7]我国艾滋病防治工作进展情况.中华人民共和国卫生部网站.2012年11月29日http://www.moh.gov.cn/publicfiles/business/htmlfiles/mohjbyfkzj/s3586/201211/5 6377. htm(accessed March 19,2013).
[8]2012年度全国法定传染病疫情概况.中华人民共和国卫生部网站.2013年3月14日.http://www.moh.gov.cn/mohjbyfkzj/s3578/201303/f02d91321f524a66a 9df357a53bd0cf0.shtml(accessed March 19,2013).
[9]Keele B F, Van Heuverswyn F, Li Y, et al. Chimpanzee reservoirs of pandemic and nonpandemic HIV-1 [J]. Science,2006,313(5786):523-526.
[10]Van Heuverswyn F, Li Y, Neel C, et al. Human immunodeficiency viruses:SIV infection in wild gorillas [J]. Nature,2006,444(7116):164.
[11]Plantier J C, Leoz M, Dickerson J E, et al. A new human immunodeficiency virus derived from gorillas [J]. Nat Med,2009,15(8):871-872.
[12]Robertson D L, Anderson J P, Bradac J A, et al. HIV-1 nomenclature proposal [J]. Science,2000,288(5463):55-56.
[13]Worobey M, Gemmel M, Teuwen D E, et al. Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960 [J]. Nature,2008,455(7213):661-664.
[14]Los Alamos National Laboratory.http://www.hiv.lanl.gov/content/sequence/ HIV/CRFs/CRFs.html (accessed Oct 31,2012).
[15]Liu Y, Li L, Bao Z, et al. Identification of a novel HIV type 1 circulating recombinant form (CRF52_01B) in Southeast Asia [J]. AIDS Res Hum Retroviruses, 2012,28(10):1357-1361.
[16]Casseb J, Katzenstein D, Winters M, et al. Serotyping HIV-1 with V3 peptides: detection of high avidity antibodies presenting clade-specific reactivity [J]. Braz J Med Biol Res,2002,35(3):369-375.
[17]Thomson M M, Perez-Alvarez L, Najera R. Molecular epidemiology of HIV-1 genetic forms and its significance for vaccine development and therapy [J]. Lancet Infect Dis,2002,2(8):461-471.
[18]Gehringer H, Von der Helm K, Seelmeir S, et al. Development and evaluation of a phenotypic assay monitoring resistance formation to protease inhibitors in HIV-1-infected patients [J]. J Virol Methods,2003,109(2):143-152.
[19]Hemelaar J, Gouws E, Ghys P D, et al. Global trends in molecular epidemiology of HIV-1 during 2000-2007 [J]. AIDS,2011,25(5):679-689.
[20]Perelson A S, Neumann A U, Markowitz M, et al. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time [J]. Science, 1996,271(5255):1582-1586.
[21]Robertson D L, Sharp P M, Mccutchan F E, et al. Recombination in HIV-1 [J]. Nature,1995,374(6518):124-126.
[22]Blackard J T, Cohen D E, Mayer K H. Human immunodeficiency virus superinfection and recombination:current state of knowledge and potential clinical consequences [J]. Clin Infect Dis,2002,34(8):1108-1114.
[23]Hemelaar J. Implications of HIV diversity for the HIV-1 pandemic [J]. J Infect, 2013,66(5):391-400.
[24]Taylor B S, Sobieszczyk M E, Mccutchan F E, et al. The challenge of HIV-1 subtype diversity [J]. N Engl J Med,2008,358(15):1590-1602.
[25]Yebra G, Rivas P, Herrero M D, et al. Clinical differences and viral diversity between newly HIV type 1-diagnosed African and non-African patients in Spain (2005-2007) [J]. AIDS Res Hum Retroviruses,2009,25(1):37-44.
[26]Bobkov A F, Kazennova E V, Selimova L M, et al. Temporal trends in the HIV-1 epidemic in Russia:predominance of subtype A [J]. J Med Virol,2004, 74(2):191-196.
[27]Williamson C, Engelbrecht S, Lambrick M, et al. HIV-1 subtypes in different risk groups in South Africa [J]. Lancet,1995,346(8977):782.
[28]Kunanusont C, Foy H M, Kreiss J K, et al. HIV-1 subtypes and male-to-female transmission in Thailand [J]. Lancet,1995,345(8957):1078-1083.
[29]Herring B L, Ge Y C, Wang B, et al. Segregation of human immunodeficiency virus type 1 subtypes by risk factor in Australia [J]. J Clin Microbiol,2003, 41(10):4600-4604.
[30]Hughes G J, Fearnhill E, Dunn D, et al. Molecular phylodynamics of the heterosexual HIV epidemic in the United Kingdom [J]. PLoS Pathog,2009, 5(9):e1000590.
[31]Op de Coul EL, Coutinho RA, van der Schoot A, et al. The impact of immigration on env HIV-1 subtype distribution among heterosexuals in the Netherlands:influx of subtype B and non-Bstrains [J]. AIDS.2001,15(17): 2277-2286.
[32]Kato S, Saito R, Hiraishi Y, et al. Differential prevalence of HIV type 1 subtype B and CRF01_AE among different sexual transmission groups in Tokyo, Japan, as revealed by subtype-specific PCR [J]. AIDS Res Hum Retroviruses,2003, 19(11):1057-1063.
[33]Iversen A K, Learn G H, Skinhoj P, et al. Preferential detection of HIV subtype C' over subtype A in cervical cells from a dually infected woman [J]. AIDS,2005, 19(9):990-993.
[34]Neilson J R, John G C, Carr J K, et al. Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya [J]. J Virol,1999, 73(5):4393-4403.
[35]Hu DJ, Vanichseni S, Mastro TD, et al. Viral load differences in early infection with two HIV-1 subtypes [J]. AIDS,2001,15(6):683-691.
[36]Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy:a collaborative re-analysis. Collaborative Group on AIDS Incubation and HIV Survival including the CASCADE EU Concerted Action. Concerted Action on SeroConversion to AIDS and Death in Europe [J]. Lancet,2000,355(9210):1131-1137.
[37]Deschamps M M, Fitzgerald D W, Pape J W, et al. HIV infection in Haiti: natural history and disease progression [J]. AIDS,2000,14(16):2515-2521.
[38]Rangsin R, Piyaraj P, Sirisanthana T, et al. The natural history of HIV-1 subtype E infection in young men in Thailand with up to 14 years of follow-up [J]. AIDS, 2007,21 (Suppl 6):S39-S46.
[39]Nelson K E, Costello C, Suriyanon V, et al. Survival of blood donors and their spouses with HIV-1 subtype E (CRF01 A_E) infection in northern Thailand, 1992-2007. AIDS,2007,21(Suppl 6):S47-S54.
[40]Kaleebu P, French N, Mahe C, et al. Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda [J]. J Infect Dis,2002,185(9):1244-1250.
[41]Geretti A M. HIV-1 subtypes:epidemiology and significance for HIV management [J]. Curr Opin Infect Dis,2006,19(1):1-7.
[42]Kwon J A, Yoon S Y, Lee C K, et al. Performance evaluation of three automated human immunodeficiency virus antigen-antibody combination immunoassays [J]. J Virol Methods,2006,133(1):20-26.
[43]Kantor R. Impact of HIV-1 pol diversity on drug resistance and its clinical implications [J]. Curr Opin Infect Dis,2006,19(6):594-606.
[44]Mcmichael A J, Borrow P, Tomaras G D, et al. The immune response during acute HIV-1 infection:clues for vaccine development [J]. Nat Rev Immunol,2010, 10(1):11-23.
[45]Kawashima Y, Pfafferott K, Frater J, et al. Adaptation of HIV-1 to human leukocyte antigen class I [J]. Nature,2009,458(7238):641-645.
[46]Bunnik E M, Euler Z, Welkers M R, et al. Adaptation of HIV-1 envelope gp120 to humoral immunity at a population level [J]. Nat Med,2010,16(9):995-997.
[47]Le Rouzic E, Benichou S. The Vpr protein from HIV-1:distinct roles along the viral life cycle [J]. Retrovirology,2005,2:11.
[48]Lu Y L, Bennett R P, Wills J W, et al. A leucine triplet repeat sequence (LXX)4 in p6gag is important for Vpr incorporation into human immunodeficiency virus type 1 particles [J]. J Virol,1995,69(11):6873-6879.
[49]Tungaturthi P K, Sawaya B E, Singh S P, et al. Role of HIV-1 Vpr in AIDS pathogenesis:relevance and implications of intravirion, intracellular and free Vpr [J]. Biomed Pharmacother,2003,57(1):20-24.
[50]Levy D N, Refaeli Y, Macgregor R R, et al. Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1 [J]. Proc Natl Acad Sci USA,1994,91(23):10873-10877.
[51]Engler A, Stangler T, Willbold D. Structure of human immunodeficiency virus type 1 Vpr(34-51) peptide in micelle containing aqueous solution [J]. Eur J Biochem, 2002,269(13):3264-3269.
[52]Engler A, Stangler T, Willbold D. Solution structure of human immunodeficiency virus type 1 Vpr(13-33) peptide in micelles [J]. Eur J Biochem, 2001,268(2):389-395.
[53]Morellet N, Bouaziz S, Petitjean P, et al. NMR structure of the HIV-1 regulatory protein VPR [J]. J Mol Biol,2003,327(1):215-227.
[54]Bourbigot S, Beltz H, Denis J, et al. The C-terminal domain of the HIV-1 regulatory protein Vpr adopts an antiparallel dimeric structure in solution via its leucine-zipper-like domain [J]. Biochem J,2005,387(Pt 2):333-341.
[55]Mahalingam S, Collman R G, Patel M, et al. Role of the conserved dipeptide Gly75 and Cys76 on HIV-1 Vpr function [J]. Virology,1995,210(2):495-500.
[56]Mahalingam S, Macdonald B, Ugen K E, et al. In vitro and in vivo tumor growth suppression by HIV-1 Vpr [J]. DNA Cell Biol,1997,16(2):137-143.
[57]Singh S P, Tomkowicz B, Lai D, et al. Functional role of residues corresponding to helical domain II (amino acids 35 to 46) of human immunodeficiency virus type 1 Vpr [J]. J Virol,2000,74(22):10650-10657.
[58]Mahalingam S, Khan S A, Murali R, et al. Mutagenesis of the putative alpha-helical domain of the Vpr protein of human immunodeficiency virus type 1: effect on stability and virion incorporation [J]. Proc Natl Acad Sci USA,1995, 92(9):3794-3798.
[59]Mahalingam S, Khan S A, Jabbar M A, et al. Identification of residues in the N-terminal acidic domain of HIV-1 Vpr essential for virion incorporation [J]. Virology,1995,207(1):297-302.
[60]Sherman M P, de Noronha C M, Pearce D, et al. Human immunodeficiency virus type 1 Vpr contains two leucine-rich helices that mediate glucocorticoid receptor coactivation independently of its effects on G(2) cell cycle arrest [J]. J Virol,2000, 74(17):8159-8165.
[61]Nie Z, Bergeron D, Subbramanian R A, et al. The putative alpha helix 2 of human immunodeficiency virus type 1 Vpr contains a determinant which is responsible for the nuclear translocation of proviral DNA in growth-arrested cells [J]. J Virol,1998,72(5):4104-4115.
[62]Subbramanian R A, Yao X J, Dilhuydy H, et al. Human immunodeficiency virus type 1 Vpr localization:nuclear transport of a viral protein modulated by a putative amphipathic helical structure and its relevance to biological activity [J]. J Mol Biol, 1998,278(1):13-30.
[63]Wang B, Ge Y C, Palasanthiran P, et al. Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair:in vivo evolution of vpr quasispecies in blood and plasma [J]. Virology,1996, 223(1):224-232.
[64]Zhou Y, Lu Y, Ratner L. Arginine residues in the C-terminus of HIV-1 Vpr are important for nuclear localization and cell cycle arrest [J]. Virology,1998,242 (2):414-424.
[65]Bourbigot S, Beltz H, Denis J, et al. The C-terminal domain of the HIV-1 regulatory protein Vpr adopts an antiparallel dimeric structure in solution via its leucine-zipper-like domain [J]. Biochem J,2005,387(Pt 2):333-341.
[66]Sawaya B E, Khalili K, Gordon J, et al. Transdominant activity of human immunodeficiency virus type 1 Vpr with a mutation at residue R73 [J]. J Virol,2000, 74(10):4877-4881.
[67]Berglez J M, Castelli L A, Sankovich S A, et al. Residues within the HFRIGC sequence of HIV-1 vpr involved in growth arrest activities [J]. Biochem Biophys Res Commun,1999,264(1):287-290.
[68]Sawaya B E, Khalili K, Gordon J, et al. Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome [J]. J Biol Chem,2000,275(45):35209-35214.
[69]Yao X J, Mouland A J, Subbramanian R A, et al. Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells [J]. J Virol,1998,72(6):4686-4693.
[70]Bischerour J, Tauc P, Leh H, et al. The (52-96) C-terminal domain of Vpr stimulates HIV-1 IN-mediated homologous strand transfer of mini-viral DNA [J]. Nucleic Acids Res,2003,31(10):2694-2702.
[71]Mahalingam S, Patel M, Collman R G, et al. The carboxy-terminal domain is essential for stability and not for virion incorporation of HIV-1 Vpr into virus particles [J]. Virology,1995,214(2):647-652.
[72]Mahalingam S, Macdonald B, Ugen K E, et al. In vitro and in vivo tumor growth suppression by HIV-1 Vpr [J]. DNA Cell Biol,1997,16(2):137-143.
[73]Wang B, Ge Y C, Palasanthiran P, et al. Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair:in vivo evolution of vpr quasispecies in blood and plasma [J]. Virology,1996, 223(1):224-232.
[74]Lum JJ, Cohen OJ, Nie Z, et al. Vpr R77Q is associated with longterm nonprogressive HIV infection and impaired induction of apoptosis [J]. J Clin Invest, 2003,111(10):1547-1554.
[75]Chui C, Cheung P K, Brumme C J, et al. HIV VprR77Q mutation does not influence clinical response of individuals initiating highly active antiretroviral therapy [J]. AIDS Res Hum Retroviruses,2006,22(7):615-618.
[76]Cavert W, Webb C H, Balfour H J. Alterations in the C-terminal region of the HIV-1 accessory gene vpr do not confer clinical advantage to subjects receiving nucleoside antiretroviral therapy [J]. J Infect Dis,2004,189(12):2181-2184.
[77]Cohen A H, Sun N C, Shapshak P, et al. Demonstration of human immunodeficiency virus in renal epithelium in HIV-associated nephropathy [J]. Mod Pathol,1989,2(2):125-128.
[78]Bruggeman L A, Ross M D, Tanji N, et al. Renal epithelium is a previously unrecognized site of HIV-1 infection [J]. J Am Soc Nephrol,2000,11(11): 2079-2087.
[79]Marras D, Bruggeman L A, Gao F, et al. Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy [J]. Nat Med,2002,8(5):522-526.
[80]Dickie P, Roberts A, Uwiera R, et al. Focal glomerulosclerosis in proviral and c-fms transgenic mice links Vpr expression to HIV-associated nephropathy [J]. Virology,2004,322(1):69-81.
[81]Zuo Y, Matsusaka T, Zhong J, et al. HIV-1 genes vpr and nef synergistically damage podocytes, leading to glomerulosclerosis [J]. J Am Soc Nephrol,2006, 17(10):2832-2843.
[82]Conaldi P G, Biancone L, Bottelli A, et al. HIV-1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas upregulation [J]. J Clin Invest,1998,102(12):2041-2049.
[83]Snyder A, Alsauskas Z C, Leventhal J S, et al. HIV-1 viral protein r induces ERK and caspase-8-dependent apoptosis in renal tubular epithelial cells [J]. AIDS,2010, 24(8):1107-1119.
[84]洪韵琳,周德江.临床病理讨论.第96例一发热、咳嗽、进行性呼吸困难[J].中华内科杂志,1986,25(7)：436-439.
[85]Palella F J, Baker R K, Moorman A C, et al. Mortality in the highly active antiretroviral therapy era:changing causes of death and disease in the HIV outpatient study [J]. J Acquir Immune Defic Syndr,2006,43(1):27-34.
[86]刘翌.艾滋病病毒分子亚型流行病学研究进展[J].中国国境卫生检疫杂志,2006,29：146-150.
[87]卓丽,唐小平,陈伟烈,等.广东省艾滋病患者HIV-1基因亚型分析[J].国际流行病学传染病学杂志,2011,38(1)：21-25.
[88]赵飞,王哲,李文杰.河南省1157份人免疫缺陷病毒1型毒株亚型分析[J].中华预防医学杂志,2008,42(6)：418-421.
[89]杨绍敏,李惠琴,陈立力,等.云南省2008-2009年HIV-1病毒株亚型分布[J].中华流行病学杂志,2012,33(8)：836-840.
[90]赵广录,于微,张娟娟,等.深圳地区1992-2008年HIV-1分子流行病学研究[J].中华流行病学杂志,2012,33(1)：82-87.
[91]Jaffe H W, Valdiserri R O, De Cock K M. The reemerging HIV/AIDS epidemic in men who have sex with men [J]. JAMA,2007,298(20):2412-2414.
[92]Tanser F, Barnighausen T, Hund L, et al. Effect of concurrent sexual partnerships on rate of new HIV infections in a high-prevalence, rural South African population:a cohort study [J]. Lancet,2011,378(9787):247-255.
[93]Centers for Disease Control and Prevention (CDC). Prevalence and awareness of HIV infection among men who have sex with men---21 cities, United States,2008. MMWR Morb Mortal Wkly Rep,2010,59(37):1201-1207.
[94]张北川,李秀芳,史同新,等.对中国男同/双性爱者人口数量与艾滋病病毒感染率的初步估测[J].中国性病艾滋病防治,2002,8(4)：197-199.
[95]王岚,王璐,丁正伟,等.中国1995-2009年艾滋病哨点监测主要人群艾滋病病毒感染流行趋势分析[J].中华流行病学杂志,2011,32(1)：20-24.
[96]Lau J T, Lin C, Hao C, et al. Public health challenges of the emerging HIV epidemic among men who have sex with men in China [J]. Public Health,2011, 125(5):260-265.
[97]Zhang X, Wang C, Hengwei W, et al. Risk factors of HIV infection and prevalence of co-infections among men who have sex with men in Beijing, China [J]. AIDS,2007,21(Suppl 8):S53-S57.
[98]Jia M, Luo H, Ma Y, et al. The HIV epidemic in Yunnan Province, China,1989-2007 [J]. J Acquir Immune Defic Syndr,2010,53 (Suppl 1):S34-S40.
[99]Gao F, Robertson D L, Morrison S G, et al. The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin [J]. J Virol,1996,70(10):7013-7029.
[100]Xiao-Jie Li, Rie Uenishi, Saiki Hase, et al. HIV/AIDS in Asia:The Shape of Epidemics and Their Molecular Epidemiology [J]. Virologica Sinica,2007,22 (6):426-433.
[101]邢辉,潘品良,苏玲,等.1996-1998年中国流行的E亚型艾滋病病毒1型毒株的分子流行病学研究[J].中国性病艾滋病防治,2002,8(4)：200-203.
[102]Wang W, Xu J, Jiang S, et al. The Dynamic Face of HIV-1 Subtypes Among Men who Have Sex with Men in Beijing, China [J]. Curr HIV Res,2011,9(2): 136-139.
[103]Wang W, Jiang S, Li S, et al. Identification of subtype B, multiple circulating recombinant forms and unique recombinants of HIV type 1 in an MSM cohort in China [J]. AIDS Res Hum Retroviruses,2008,24(10):1245-1254.
[104]Zhang X, Li S, Li X, et al. Characterization of HIV-1 subtypes and viral antiretroviral drug resistance in men who have sex with men in Beijing, China [J]. AIDS,2007,21 Suppl 8:S59-S65.
[105]邵一鸣,戴玉林,邢辉.HIV-1和HIV-2混合感染的发现[J].中华实验和临床病毒学杂志,1999,13(4)：383.
[106]Renjifo B, Gilbert P, Chaplin B, et al. Preferential in-utero transmission of HIV-1 subtype C as compared to HIV-1 subtype A or D [J]. AIDS,2004,18(12): 1629-1636.
[107]John-Stewart G C, Nduati R W, Rousseau C M, et al. Subtype C Is associated with increased vaginal shedding of HIV-1 [J]. J Infect Dis,2005,192(3):492-496.
[108]Hudgens M G, Longini I J, Vanichseni S, et al. Subtype-specific transmission probabilities for human immunodeficiency virus type 1 among injecting drug users in Bangkok, Thailand [J]. Am J Epidemiol,2002,155(2):159-168.
[109]Costello C, Nelson K E, Suriyanon V, et al. HIV-1 subtype E progression among northern Thai couples:traditional and non-traditional predictors of survival [J]. Int. J. Epidemiol.,2005,34(3):577-584.
[110]Kaleebu P, French N, Mahe C, et al. Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda [J]. J Infect Dis,2002,185(9):1244-1250.
[111]Baeten J M, Chohan B, Lavreys L, et al. HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads [J]. J Infect Dis,2007,195(8):1177-1180.
[112]Huang W, Eshleman S H, Toma J, et al. Coreceptor tropism in human immunodeficiency virus type 1 subtype D:high prevalence of CXCR4 tropism and heterogeneous composition of viral populations [J]. J Virol,2007,81(15):7885-7893.
[113]Neilson J R, John G C, Carr J K, et al. Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya [J]. J Virol,1999, 73(5):4393-4403.
[114]Fischetti L, Opare-Sem O, Candotti D, et al. Higher viral load may explain the dominance of CRF02_AG in the molecular epidemiology of HIV in Ghana [J]. AIDS, 2004,18(8):1208-1210.
[115]Hu D J, Vanichseni S, Mastro T D, et al. Viral load differences in early infection with two HIV-1 subtypes [J]. AIDS,2001,15(6):683-691.
[116]Peters PJ, Moore DM, Mermin J, et al. Antiretroviral therapy improves renal function among HIV-infected Ugandans [J]. Kidney Int.,2008,74(7):925-929.
[117]Alexander C S, Montessori V, Wynhoven B, et al. Prevalence and response to antiretroviral therapy of non-B subtypes of HIV in antiretroviral-naive individuals in British Columbia [J]. Antivir Ther,2002,7(1):31-35.
[118]Bocket L, Cheret A, Deuffic-Burban S, et al. Impact of human immunodeficiency virus type 1 subtype on first-line antiretroviral therapy effectiveness [J]. Antivir Ther,2005,10(2):247-254.
[119]Atlas A, Granath F, Lindstrom A, et al. Impact of HIV type 1 genetic subtype on the outcome of antiretroviral therapy [J]. AIDS Res Hum Retroviruses,2005, 21(3):221-227.
[120]Fischer A, Lejczak C, Lambert C, et al. Is the Vpr R77Q mutation associated with long-term non-progression of HIV infection? [J]. AIDS,2004,18(9):1346-1347.
[121]Mologni D, Citterio P, Menzaghi B, et al. Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients [J]. AIDS,2006,20(4):567-574.
[122]Brenner C, Kroemer G. The mitochondriotoxic domain of Vpr determines HIV-1 virulence [J]. J Clin Invest,2003,111(10):1455-1457.
[123]Jacotot E, Ravagnan L, Loeffler M, et al. The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore [J]. J Exp Med,2000,191(1):33-46.
[124]Gaynor E M, Chen I S. Analysis of apoptosis induced by HIV-1 Vpr and examination of the possible role of the hHR23A protein [J]. Exp Cell Res,2001, 267(2):243-257.
[125]Rodes B, Toro C, Paxinos E, et al. Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection [J]. AIDS,2004,18(8):1109-1116.
[126]Green DR, Kroemer G. The pathophysiology of mitochondrial cell death [J]. Science,2004,305(5684):626-629.
[127]Jian H, Zhao L J. Pro-apoptotic activity of HIV-1 auxiliary regulatory protein Vpr is subtype-dependent and potently enhanced by nonconservative changes of the leucine residue at position 64 [J]. J Biol Chem,2003,278(45):44326-44330.
[128]Cartas M, Singh S P, Serio D, et al. Intravirion display of a peptide corresponding to the dimer structure of protease attenuates HIV-1 replication [J]. DNA Cell Biol,2001,20(12):797-805.
[1]Yuan X, Matsuda Z, Matsuda M, et al. Human immunodeficiency virus vpr gene encodes a virion-associated protein [J]. AIDS Res Hum Retroviruses,1990, 6(11):1265-1271.
[2]Cohen EA, Terwilliger EF, Jalinoos Y, et al. Identification of HIV-1 vpr product and function [J]. J Acquir Immune Defic Syndr,1990,3(1):11-18.
[3]Planelles V, Jowett JB, Li QX, et al. Vpr-induced cell cycle arrest is conserved among primate lentiviruses [J]. J Virol,1996,70(4):2516-2524.
[4]Emerman M. HIV-1, Vpr and the cell cycle. Curr Biol 1996,6(9):1096-1103.
[5]Feldherr CM, Feldherr AB. The nuclear membrane as a barrier to the free diffusion of proteins [J]. Nature,1960,185:250-251.
[6]Lewis PF, Emerman M. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus [J]. J Virol,1994,68(1):510-516.
[7]Bukrinsky MI, Sharova N, Dempsey MP, et al. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes [J]. Proc Natl Acad Sci USA, 1992,89(14):6580-6584.
[8]Lu YL, Spearman P, Ratner L. Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions [J]. J Virol,1993, 67(11):6542-6550.
[9]Di Marzio P, Choe S, Ebright M, et al. Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr [J]. J Virol,1995,69(12):7909-7916.
[10]Gallay P, Hope T, Chin D, et al. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway [J]. Proc Natl Acad Sci USA,1997,94(18):9825-9830.
[11]Dismuke DJ, Aiken C. Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex [J]. J Virol,2006,80(8):3712-3720.
[12]Gorlich D. Nuclear protein import [J]. Curr Opin Cell Biol 1997,9(3):412-419.
[13]Herold A, Truant R, Wiegand H, et al. Determination of the functional domain organization of the importin alpha nuclear import factor [J]. J Cell Biol,1998, 143(2):309-318.
[14]Kobe B. Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha [J]. Nat Struct Biol,1999, 6(4):388-397.
[15]Moore MS, Blobel G. The GTP-binding protein Ran/TC4 is required for protein import into the nucleus [J]. Nature,1993,365(6447):661-663.
[16]Melchior F, Paschal B, Evans J, et al. Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential transport factor [J]. J Cell Biol,1993,123(6 Pt 2):1649-1659.
[17]Paschal BM, Gerace L. Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62 [J]. J Cell Biol,1995, 129(4):925-937.
[18]Kotera I, Sekimoto T, Miyamoto Y, et al. Importin alpha transports CaMKIV to the nucleus without utilizing importin beta [J]. Embo J,2005,24(5):942-951.
[19]Takizawa CG, Weis K, Morgan DO. Ran-independent nuclear import of cyclin B1-Cdc2 by importin beta [J]. Proc Natl Acad Sci USA,1999,96(14):7938-7943.
[20]Siomi H, Dreyfuss G. A nuclear localization domain in the hnRNP A1 protein [J]. J Cell Biol,1995,129(3):551-560.
[21]Michael WM, Choi M, Dreyfuss G. A nuclear export signal in hnRNP Al:a signal-mediated, temperature-dependent nuclear protein export pathway [J]. Cell, 1995,83(3):415-422.
[22]Aitchison JD, Blobel G, Rout MP. Kap104p:a karyopherin involved in the nuclear transport of messenger RNA binding proteins [J]. Science,1996, 274(5287):624-627.
[23]Nakielny S, Siomi MC, Siomi H, et al. Transportin:nuclear transport receptor of a novel nuclear protein import pathway [J]. Exp Cell Res,1996,229(2):261-266.
[24]Jenkins Y, McEntee M, Weis K, et al. Characterization of HIV-1 vpr nuclear import:analysis of signals and pathways [J]. J Cell Biol,1998,143(4):875-885.
[25]Efthymiadis A, Shao H, Hubner S, et al. Kinetic characterization of the human retinoblastoma protein bipartite nuclear localization sequence (NLS) in vivo and in vitro. A comparison with the SV40 large T-antigen NLS [J]. J Biol Chem,1997, 272(35):22134-22139.
[26]Jans DA, Jans P, Julich T, et al. Intranuclear binding by the HIV-1 regulatory protein VPR is dependent on cytosolic factors [J]. Biochem Biophys Res Commun, 2000,270(3):1055-1062.
[27]Nitahara-Kasahara Y, Kamata M, Yamamoto T, et al. Novel nuclear import of Vpr promoted by importin alpha is crucial for human immunodeficiency virus type 1 replication in macrophages [J]. J Virol,2007,81(10):5284-5293.
[28]Kamata M, Nitahara-Kasahara Y, Miyamoto Y, et al. Importinalpha promotes passage through the nuclear pore complex of human immunodeficiency virus type 1 Vpr [J]. J Virol,2005,79(6):3557-3564.
[29]Connor RI, Chen BK, Choe S, et al. Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes [J]. Virology, 1995,206(2):935-944.
[30]Blomer U, Naldini L, Kafri T, et al. Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector [J]. J Virol,1997,71(9):6641-6649.
[31]Jacquot G, Le Rouzic E, David A,et al. Localization of HIV-1 Vpr to the nuclear envelope:impact on Vpr functions and virus replication in macrophages [J]. Retrovirology,2007,4:84.
[32]Caly L, Saksena NK, Piller SC, et al. Impaired nuclear import and viral incorporation of Vpr derived from a HIV long-term non-progressor [J]. Retrovirology, 2008,5:67.
[33]Popov S, Rexach M, Ratner L, et al. Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex [J]. J Biol Chem,1998, 273(21):13347-13352.
[34]Keele BF, Giorgi EE, Salazar-Gonzalez JF, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection [J]. Proc Natl Acad Sci USA,2008,105(21):7552-7557.
[35]Fischer W, Ganusov VV, Giorgi EE, et al. Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing [J]. PLoS One,2010,5(8):e12303.
[36]Iijima S, Nitahara-Kasahara Y, Kimata K, et al. Nuclear localization of Vpr is crucial for the efficient replication of HIV-1 in primary CD4+T cells [J]. Virology, 2004,327(2):249-261.
[37]Yamashita M, Perez O, Hope TJ, et al. Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells [J]. PLoS Pathog 2007, 3(10):1502-1510.
[38]Morellet N, Bouaziz S, Petitjean P, et al. NMR structure of the HIV-1 regulatory protein VPR [J]. J Mol Biol,2003,327(1):215-227.
[39]Singh SP, Tomkowicz B, Lai D, et al. Functional role of residues corresponding to helical domain II (amino acids 35 to 46) of human immunodeficiency virus type 1 Vpr [J]. J Virol,2000,74(22):10650-10657.
[40]Mahalingam S, Ayyavoo V, Patel M, et al. Nuclear import, virion incorporation, and cell cycle arrest/differentiation are mediated by distinct functional domains of human immunodeficiency virus type 1 Vpr [J]. J Virol,1997,71(9):6339-6347.
[41]Fritz JV, Didier P, Clamme JP, et al. Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging [J]. Retrovirology,2008,5:87.
[42]Agostini I, Popov S, Li J, et al. Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import of the viral preintegration complex [J]. Exp Cell Res, 2000,259(2):398-403.
[43]Kamata M, Aida Y. Two putative alpha-helical domains of human immunodeficiency virus type 1 Vpr mediate nuclear localization by at least two mechanisms [J]. J Virol,2000,74(15):7179-7186.
[44]Le Rouzic E, Mousnier A, Rustum C, et al. Docking of HIV-1 Vpr to the nuclear envelope is mediated by the interaction with the nucleoporin hCGl. J Biol Chem, 2002,277(47):45091-45098.
[45]Fouchier RA, Meyer BE, Simon JH, et al. Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex [J]. J Virol, 1998,72(7):6004-6013.
[46]Vodicka MA, Koepp DM, Silver PA,et al. HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection [J]. Genes Dev,1998, 12(2):175-185.
[47]Rexach M, Blobel G. Protein import into nuclei:association and dissociation reactions involving transport substrate, transport factors, and nucleoporins [J]. Cell, 1995,83(5):683-692.
[48]Kutay U, Izaurralde E, Bischoff FR, et al. Dominant-negative mutants of importin-beta block multiple pathways of import and export through the nuclear pore complex [J]. Embo J,1997,16(6):1153-1163.
[49]Karni O, Friedler A, Zakai N, et al. A peptide derived from the N-terminal region of HIV-1 Vpr promotes nuclear import in permeabilized cells:elucidation of the NLS region of the Vpr [J]. FEBS Lett,1998,429(3):421-425.
[50]Zhou Y, Lu Y, Ratner L. Arginine residues in the C-terminus of HIV-1 Vpr are important for nuclear localization and cell cycle arrest [J]. Virology,1998, 242(2):414-424.
[51]Levy DN, Refaeli Y, Weiner DB. Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency [J]. J Virol,1995,69(2):1243-1252.
[52]Wang L, Mukherjee S, Jia F, et al. Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Spl and trans-activation of viral long terminal repeat [J]. J Biol Chem,1995,270(43): 25564-25569.
[53]McAllister JJ, Phillips D, Millhouse S, et al. Analysis of the HIV-1 LTR NF-kappaB-proximal Sp site Ⅲ:evidence for cell type-specific gene regulation and viral replication [J]. Virology,2000,274(2):262-277.
[54]Vanitharani R, Mahalingam S, Rafaeli Y, et al. HIV-1 Vpr transactivates LTR-directed expression through sequences present within -278 to-176 and increases virus replication in vitro [J]. Virology,2001,289(2):334-342.
[55]Agostini I, Navarro JM, Rey F, et al. The human immunodeficiency virus type 1 Vpr transactivator:cooperation with promoter-bound activator domains and binding to TFIIB [J]. J Mol Biol,1996,261(5):599-606.
[56]Felzien LK, Woffendin C, Hottiger MO, et al. HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator [J]. Proc Natl Acad Sci USA 1998,95(9):5281-5286.
[57]Sawaya BE, Khalili K, Rappaport J, et al. Suppression of HIV-1 transcription and replication by a Vpr mutant [J]. Gene Ther,1999,6(5):947-950.
[58]Sawaya BE, Khalili K, Gordon J, et al. Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome [J]. J Biol Chem,2000,275(45):35209-35214.
[59]Refaeli Y, Levy DN, Weiner DB. The glucocorticoid receptor type Ⅱ complex is a target of the HIV-1 vpr gene product [J]. Proc Natl Acad Sci USA,1995,92(8): 3621-3625.
[60]Kino T, Gragerov A, Kopp JB, et al. The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor [J]. J Exp Med,1999,189(1):51-62.
[61]Sherman MP, de Noronha CM, Pearce D, et al. Human immunodeficiency virus type 1 Vpr contains two leucine-rich helices that mediate glucocorticoid receptor coactivation independently of its effects on G(2) cell cycle arrest [J]. J Virol,2000, 74(17):8159-8165.
[62]Kino T, Gragerov A, Slobodskaya O, et al. Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces transcription of the HIV-1 and glucocorticoid-responsive promoters by binding directly to p300/CBP coactivators [J]. J Virol,2002,76(19):9724-9734.
[63]Muthumani K, Choo AY, Zong WX, et al. The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1 [J]. Nat Cell Biol,2006,8(2):170-179.
[64]Chatterton RT Jr, Green D, Harris S, et al. Longitudinal study of adrenal steroids in a cohort of HIV-infected patients with hemophilia [J]. J Lab Clin Med,1996, 127(6):545-552.
[65]Russo FO, Patel PC, Ventura AM, et al. HIV-1 long terminal repeat modulation by glucocorticoids in monocytic and lymphocytic cell lines [J]. Virus Res,1999, 64(1):87-94.
[66]Kino T, Kopp JB, Chrousos GP. Glucocorticoids suppress human immunodeficiency virus type-1 long terminal repeat activity in a cell type-specific, glucocorticoid receptor-mediated fashion:direct protective effects at variance with clinical phenomenology [J]. J Steroid Biochem Mol Biol,2000,75:283-290.
[67]Laurence J, Sellers MB, Sikder SK. Effect of glucocorticoids on chronic human immunodeficiency virus (HIV) infection and HIV promoter mediated transcription [J]. Blood,1989,74(1):291-297.
[68]Kinter AL, Biswas P, Alfano M, et al. Interleukin-6 and glucocorticoids synergistically induce human immunodeficiency virus type-1 expression in chronically infected U1 cells by a long terminal repeat independent post-transcriptional mechanism [J]. Mol Med,2001,7:668-678.
[69]Hoshino S, Konishi M, Mori M, et al. HIV-1 Vpr induces TLR4/MyD88-mediated IL-6 production and reactivates viral production from latency [J]. J Leukoc Biol,2010,87(6):1133-1143.
[70]Bressler P, Poli G, Justement JS, et al. Glucocorticoids synergize with tumor necrosis factor alpha in the induction of HIV expression from a chronically infected promonocytic cell line [J]. AIDS Res Hum Retroviruses,1993,9(6):547-551.
[71]Schafer EA, Venkatachari NJ, Ayyavoo V. Antiviral effects of mifepristone on human immunodeficiency virus type-1 (HIV-1):targeting Vpr and its cellular partner, the glucocorticoid receptor (GR) [J]. Antiviral Res,2006,72(3):224-232.
[72]Wiegers K, Schwarck D, Reimer R, et al. Activation of the glucocorticoid receptor releases unstimulated PBMCs from an early block in HIV-1 replication [J]. Virology,2008,375(1):73-84.
[73]Fletcher TM, Brichacek B, Sharova N, et al. Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIV(SM) [J]. Embo J,1996,15(22):6155-6165.
[74]Subbramanian RA, Kessous-Elbaz A, Lodge R, et al. Human immunodeficiency virus type 1 Vpr is a positive regulator of viral transcription and infectivity in primary human macrophages [J]. J Exp Med,1998,187(7):1103-1111.
[75]Wen X, Duus KM, Friedrich TD, et al. The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4Acontaining ubiquitin ligase complex using VprBP/DCAF1 as an adaptor [J]. J Biol Chem,2007,282(37):27046-27057.
[76]DeHart JL, Zimmerman ES, Ardon O, et al. HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system [J]. Virol J, 2007,4:57.
[77]Zhao LJ, Mukherjee S, Narayan O. Biochemical mechanism of HIV-I Vpr function Specific interaction with a cellular protein [J]. J Biol Chem,1994,269(22): 15577-15582.
[78]Casey L, Wen X, de Noronha CM:The functions of the HIV1 protein Vpr and its action through the DCAF1.DDB1.Cullin4 ubiquitin ligase [J]. Cytokine,2010,51(1): 1-9.
[79]Zimmerman E, Sherman M, Blackett J, et al. Human immunodeficiency virus type 1 Vpr induces DNA replication stress in vitro and in vivo [J]. J Virol,2006, 80(21):10407-10418.
[80]Goh WC, Rogel ME, Kinsey CM, et al. HIV-1 Vpr increases viral expression by manipulation of the cell cycle:a mechanism for selection of Vpr in vivo [J]. Nat Med, 1998,4(1):65-71.
[81]Igarashi T, Brown CR, Endo Y, et al. Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans [J]. Proc Natl Acad Sci USA,2001, 98(2):658-663.
[82]Bergamaschi A, Ayinde D, David A, et al. The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection [J]. J Virol,2009,83(10):4854-4860.
[83]Cosenza MA, Zhao ML, Lee SC. HIV-1 expression protects macrophages and microglia from apoptotic death [J]. Neuropathol Appl Neurobiol,2004,30(5):478-490.
[84]Fernandez Larrosa PN, Croci DO, Riva DA, et al. Apoptosis resistance in HIV-1 persistently-infected cells is independent of active viral replication and involves modulation of the apoptotic mitochondrial pathway [J]. Retrovirology,2008,5:19.
[85]Fukumori T, Akari H, Yoshida A, et al. Regulation of cell cycle and apoptosis by human immunodeficiency virus type 1 Vpr [J]. Microbes Infect,2000,2(9):1011-1017.
[86]Conti L, Rainaldi G, Matarrese P, et al. The HIV-1 vpr protein acts as a negative regulator of apoptosis in a human lymphoblastoid T cell line:possible implications for the pathogenesis of AIDS [J]. J Exp Med,1998,187(3):403-413.
[87]Rostad SW, Sumi SM, Shaw CM, et al. Human immunodeficiency virus (HIV) infection in brains with AIDS-related leukoencephalopathy [J]. AIDS Res Hum Retroviruses,1987,3(4):363-373.
[88]McArthur JC. HIV dementia:an evolving disease [J]. J Neuroimmunol,2004, 157(1-2):3-10.
[89]Porwit A, Parravicini C, Petren AL, et al. Cell association of HIV in AIDS-related encephalopathy and dementia [J]. Apmis,1989,97(1):79-90.
[90]Williams KC, Corey S, Westmoreland SV, et al. Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques:implications for the neuropathogenesis of AIDS [J]. J Exp Med, 2001,193(8):905-915.
[91]Glass JD, Fedor H, Wesselingh SL, et al. Immunocytochemical quantitation of human immunodeficiency virus in the brain:correlations with dementia [J]. Ann Neurol,1995,38(5):755-762.
[92]Fischer-Smith T, Tedaldi EM, Rappaport J. CD163/CD16 coexpression by circulating monocytes/macrophages in HIV:potential biomarkers for HIV infection and AIDS progression [J]. AIDS Res Hum Retroviruses,2008,24(3):417-421.
[93]Fischer-Smith T, Croul S, Sverstiuk AE, et al. CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia:perivascular accumulation and reservoir of HIV infection [J]. J Neurovirol,2001,7(6):528-541.
[94]Fischer-Smith T, Rappaport J. Evolving paradigms in the pathogenesis of HIV-1-associated dementia [J]. Expert Rev Mol Med,2005,7(27):1-26.
[95]Wheeler ED, Achim CL, Ayyavoo V. Immunodetection of human immunodeficiency virus type 1 (HIV-1) Vpr in brain tissue of HIV-1 encephalitic patients [J]. J Neurovirol,2006,12(3):200-210.
[96]Jones GJ, Barsby NL, Cohen EA, et al. HIV-1 Vpr causes neuronal apoptosis and in vivo neurodegeneration [J]. J Neurosci,2007,27(14):3703-3711.
[97]Sabbah EN, Roques BP. Critical implication of the (70-96) domain of human immunodeficiency virus type 1 Vpr protein in apoptosis of primary rat cortical and striatal neurons [J]. J Neurovirol,2005,11(6):489-502.
[98]Patel CA, Mukhtar M, Pomerantz RJ. Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cells [J]. J Virol,2000,74(20):9717-9726.
[99]Acheampong E, Mukhtar M, Parveen Z, et al. Ethanol strongly potentiates apoptosis induced by HIV-1 proteins in primary human brain microvascular endothelial cells [J]. Virology,2002,304(2):222-234.
[100]Rom I, Deshmane SL, Mukerjee R, et al. HIV-1 Vpr deregulates calcium secretion in neural cells [J]. Brain Res,2009,1275:81-86.
[101]Hogan TH, Nonnemacher MR, Krebs FC, et al. HIV-1 Vpr binding to HIV-1 LTR C/EBP cis-acting elements and adjacent regions is sequence-specific [J]. Biomed Pharmacother,2003,57(1):41-48.
[102]Burdo TH, Nonnemacher M, Irish BP, et al. High-affinity interaction between HIV-1 Vpr and specific sequences that span the C/EBP and adjacent NF-kappaB sites within the HIV-1 LTR correlate with HIV-1-associated dementia [J]. DNA Cell Biol, 2004,23(4):261-269.
[103]Kilareski EM, Shah S, Nonnemacher MR, et al. Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage [J]. Retrovirology,2009, 6:118.
[104]Wyatt CM, Rosenstiel PE, Klotman PE. HIV-associated nephropathy [J]. Contrib Nephrol,2008,159:151-161.
[105]Kopp J, Smith M, Nelson G, et al. MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis [J]. Nat Genet,2008,40(10):1175-1184.
[106]Tang P, Jerebtsova M, Przygodzki R, et al. Fibroblast growth factor-2 increases the renal recruitment and attachment of HIV-infected mononuclear cells to renal tubular epithelial cells [J]. Pediatr Nephrol,2005,20(12):1708-1716.
[107]Dickie P, Roberts A, Uwiera R, et al. Focal glomerulosclerosis in proviral and c-frms transgenic mice links Vpr expression to HIV-associated nephropathy [J]. Virology,2004,322(1):69-81.
[108]Zhong J, Zuo Y, Ma J, et al. Expression of HIV-1 genes in podocytes alone can lead to the full spectrum of HIV-1-associated nephropathy [J]. Kidney Int,2005, 68(3):1048-1060.
[109]Muthumani K, Bagarazzi M, Conway D, et al. Inclusion of Vpr accessory gene in a plasmid vaccine cocktail markedly reduces Nef vaccine effectiveness in vivo resulting in CD4 cell loss and increased viral loads in rhesus macaques [J]. J Med Primatol,2002,31(4-5):179-185.
[110]Moon HS, Yang JS. Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells [J]. Mol Cells,2006,21(1):7-20.
[111]Azad AA. Could Nef and Vpr proteins contribute to disease progression by promoting depletion of bystander cells and prolonged survival of HIV-infected cells? [J] Biochem Biophys Res Commun,2000,267(3):677-685.
[112]Yasuda J, Miyao T, Kamata M, et al. T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr gene [J]. Virology,2001,285(2): 181-192.
[113]Li G, Park HU, Liang D, et al. Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R [J]. Retrovirology,2010,7:59.
[114]Muthumani K, Zhang D, Hwang DS, et al. Adenovirus encoding HIV-1 Vpr activates caspase 9 and induces apoptotic cell death in both p53 positive and negative human tumor cell lines [J]. Oncogene,2002,21(30):4613-4625.
[115]Majumder B, Venkatachari NJ, Schafer EA, et al. Dendritic cells infected with vpr-positive human immunodeficiency virus type 1 induce CD8+T-cell apoptosis via upregulation of tumor necrosis factor alpha [J]. J Virol,2007,81(14):7388-7399.
[116]Richard J, Sindhu S, Pham TN, et al. HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell-mediated killing [J]. Blood,2010,115(7):1354-1363.
[117]Majumder B, Venkatachari NJ, O'Leary S, et al. Infection with Vprpositive mhuman immunodeficiency virus type 1 impairs NK cell function indirectly through cytokine dysregulation of infected target cells [J]. J Virol,2008,82(14):7189-7200.
[118]Majumder B, Janket ML, Schafer EA, et al. Human immunodeficiency virus type 1 Vpr impairs dendritic cell maturation and T-cell activation:implications for viral immune escape [J]. J Virol,2005,79(13):7990-8003.
[119]Venkatachari NJ, Majumder B, Ayyavoo V. Human immunodeficiency virus (HIV) type 1 Vpr induces differential regulation of T cell costimulatory molecules: direct effect of Vpr on T cell activation and immune function [J]. Virology,2007, 358(2):347-356.
[120]Lang SM, Weeger M, Stahl-Hennig C, et al. Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus [J]. J Virol,1993,67(2):902-912.
[121]Tzitzivacos DB, Tiemessen CT, Stevens WS, et al. Viral genetic determinants of nonprogressive HIV type 1 subtype C infection in antiretroviral drug-naive children [J]. AIDS Res Hum Retroviruses,2009,25(11):1141-1148.
[122]Aquaro S, Svicher V, Schols D, et al. Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages:new therapeutic strategies [J]. J Leukoc Biol,2006,80(5):1103-1110.
[123]Dutta T, Agashe HB, Garg M, et al. Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro [J]. J Drug Target,2007,15(1):89-98.
[124]Swingler S, Mann AM, Zhou J, et al. Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein [J]. PLoS Pathog,2007, 3(9):1281-1290.
[125]Kapasi AA, Coscia SA, Pandya MP, et al. Morphine modulates HIV-1 gp160-induced murine macrophage and human monocyte apoptosis by disparate ways [J]. J Neuroimmunol,2004,148(1-2):86-96.
[126]Li G, Bukrinsky M, Zhao RY. HIV-1 viral protein R (Vpr) and its interactions with host cell [J]. Curr HIV Res,2009,7(2):178-183.
[127]Liang D, Benko Z, Agbottah E, et al. Anti-vpr activities of heat shock protein 27 [J]. Mol Med,2007,13(5-6):229-239.
[128]Iordanskiy S, Zhao Y, Dubrovsky L, et al. Heat shock protein 70 protects cells from cell cycle arrest and apoptosis induced by human immunodeficiency virus type 1 viral protein R [J]. J Virol,2004,78(18):9697-9704.
[129]Yedavalli VS, Shih HM, Chiang YP, et al. Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1 [J]. J Virol,2005, 79:13735-13746.
[130]Gibellini D, Re MC, Ponti C, et al. HIV-1 Tat protein concomitantly down-regulates apical caspase-10 and up-regulates c-FLIP in lymphoid T cells:a potential molecular mechanism to escape TRAIL cytotoxicity [J]. J Cell Physiol,2005, 203(3):547-556.
[131]Haffar OK, Smithgall MD, Popov S, et al. CNI-H0294, a nuclear importation inhibitor of the human immunodeficiency virus type 1 genome, abrogates virus replication in infected activated peripheral blood mononuclear cells [J]. Antimicrob Agents Chemother,1998,42:1133-1138.
[132]Paxton W, Connor RI, Landau NR. Incorporation of Vpr into human immunodeficiency virus type 1 virions:requirement for the p6 region of gag and mutational analysis [J]. J Virol,1993,67(12):7229-7237.
[133]Ao Z, Yu Z, Wang L, et al. Vprl4-88-Apobec3G fusion protein is efficiently incorporated into Vif-positive HIV-1 particles and inhibits viral infection [J]. PLoS ONE,2008,3(4):e1995.
[134]Mariani R, Chen D, Schrofelbauer B, et al. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif [J]. Cell,2003,114:21-31.
[135]Stewart SA, Poon B, Jowett JB, et al. Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells [J]. Proc Natl Acad Sci USA,1999,96(21): 12039-12043.
[136]Ayyavoo V, Mahboubi A, Mahalingam S, et al. HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B [J]. Nat Med, 1997,3(10):1117-1123.
[137]Shimura M, Tanaka Y, Nakamura S, et al. Micronuclei formation and aneuploidy induced by Vpr, an accessory gene of human immunodeficiency virus type 1 [J]. Faseb J,1999,13(6):621-637.
[2]Center for Disease Control (CDC). Pneumocystis pneumonia Los Angeles [J]. MMWR Morb Mortal Wkly Rep,1981,30(21):250-252.
[3]Pincock S. Francoise Barre-Sinoussi:shares Nobel Prize for discovery of HIV [J]. Lancet,2008,372(9647):1377.
[4]临床病理讨论.第96例—发热、咳嗽、进行性呼吸困难[J].中华内科杂志,1986,25(7)：436-439.
[5]UNAIDS. Report on the global AIDS epidemic 2012. Geneva:UNAIDS, 2012;http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/ 2012/gr2012/20121120_UNAIDS_Global_Report_2012_with_annexes_en.pdf
[6]中华人民共和国卫生部,联合国艾滋病规划署,世界卫生组织.2011年中国艾滋病疫情评估[J].中国艾滋病性病,2011,18(1)：1-5.
[7]我国艾滋病防治工作进展情况.中华人民共和国卫生部网站.2012年11月29日http://www.moh.gov.cn/publicfiles/business/htmlfiles/mohjbyfkzj/s3586/201211/5 6377. htm(accessed March 19,2013).
[8]2012年度全国法定传染病疫情概况.中华人民共和国卫生部网站.2013年3月14日.http://www.moh.gov.cn/mohjbyfkzj/s3578/201303/f02d91321f524a66a 9df357a53bd0cf0.shtml(accessed March 19,2013).
[9]Keele B F, Van Heuverswyn F, Li Y, et al. Chimpanzee reservoirs of pandemic and nonpandemic HIV-1 [J]. Science,2006,313(5786):523-526.
[10]Van Heuverswyn F, Li Y, Neel C, et al. Human immunodeficiency viruses:SIV infection in wild gorillas [J]. Nature,2006,444(7116):164.
[11]Plantier J C, Leoz M, Dickerson J E, et al. A new human immunodeficiency virus derived from gorillas [J]. Nat Med,2009,15(8):871-872.
[12]Robertson D L, Anderson J P, Bradac J A, et al. HIV-1 nomenclature proposal [J]. Science,2000,288(5463):55-56.
[13]Worobey M, Gemmel M, Teuwen D E, et al. Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960 [J]. Nature,2008,455(7213):661-664.
[14]Los Alamos National Laboratory.http://www.hiv.lanl.gov/content/sequence/ HIV/CRFs/CRFs.html (accessed Oct 31,2012).
[15]Liu Y, Li L, Bao Z, et al. Identification of a novel HIV type 1 circulating recombinant form (CRF52_01B) in Southeast Asia [J]. AIDS Res Hum Retroviruses, 2012,28(10):1357-1361.
[16]Casseb J, Katzenstein D, Winters M, et al. Serotyping HIV-1 with V3 peptides: detection of high avidity antibodies presenting clade-specific reactivity [J]. Braz J Med Biol Res,2002,35(3):369-375.
[17]Thomson M M, Perez-Alvarez L, Najera R. Molecular epidemiology of HIV-1 genetic forms and its significance for vaccine development and therapy [J]. Lancet Infect Dis,2002,2(8):461-471.
[18]Gehringer H, Von der Helm K, Seelmeir S, et al. Development and evaluation of a phenotypic assay monitoring resistance formation to protease inhibitors in HIV-1-infected patients [J]. J Virol Methods,2003,109(2):143-152.
[19]Hemelaar J, Gouws E, Ghys P D, et al. Global trends in molecular epidemiology of HIV-1 during 2000-2007 [J]. AIDS,2011,25(5):679-689.
[20]Perelson A S, Neumann A U, Markowitz M, et al. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time [J]. Science, 1996,271(5255):1582-1586.
[21]Robertson D L, Sharp P M, Mccutchan F E, et al. Recombination in HIV-1 [J]. Nature,1995,374(6518):124-126.
[22]Blackard J T, Cohen D E, Mayer K H. Human immunodeficiency virus superinfection and recombination:current state of knowledge and potential clinical consequences [J]. Clin Infect Dis,2002,34(8):1108-1114.
[23]Hemelaar J. Implications of HIV diversity for the HIV-1 pandemic [J]. J Infect, 2013,66(5):391-400.
[24]Taylor B S, Sobieszczyk M E, Mccutchan F E, et al. The challenge of HIV-1 subtype diversity [J]. N Engl J Med,2008,358(15):1590-1602.
[25]Yebra G, Rivas P, Herrero M D, et al. Clinical differences and viral diversity between newly HIV type 1-diagnosed African and non-African patients in Spain (2005-2007) [J]. AIDS Res Hum Retroviruses,2009,25(1):37-44.
[26]Bobkov A F, Kazennova E V, Selimova L M, et al. Temporal trends in the HIV-1 epidemic in Russia:predominance of subtype A [J]. J Med Virol,2004, 74(2):191-196.
[27]Williamson C, Engelbrecht S, Lambrick M, et al. HIV-1 subtypes in different risk groups in South Africa [J]. Lancet,1995,346(8977):782.
[28]Kunanusont C, Foy H M, Kreiss J K, et al. HIV-1 subtypes and male-to-female transmission in Thailand [J]. Lancet,1995,345(8957):1078-1083.
[29]Herring B L, Ge Y C, Wang B, et al. Segregation of human immunodeficiency virus type 1 subtypes by risk factor in Australia [J]. J Clin Microbiol,2003, 41(10):4600-4604.
[30]Hughes G J, Fearnhill E, Dunn D, et al. Molecular phylodynamics of the heterosexual HIV epidemic in the United Kingdom [J]. PLoS Pathog,2009, 5(9):e1000590.
[31]Op de Coul EL, Coutinho RA, van der Schoot A, et al. The impact of immigration on env HIV-1 subtype distribution among heterosexuals in the Netherlands:influx of subtype B and non-Bstrains [J]. AIDS.2001,15(17): 2277-2286.
[32]Kato S, Saito R, Hiraishi Y, et al. Differential prevalence of HIV type 1 subtype B and CRF01_AE among different sexual transmission groups in Tokyo, Japan, as revealed by subtype-specific PCR [J]. AIDS Res Hum Retroviruses,2003, 19(11):1057-1063.
[33]Iversen A K, Learn G H, Skinhoj P, et al. Preferential detection of HIV subtype C' over subtype A in cervical cells from a dually infected woman [J]. AIDS,2005, 19(9):990-993.
[34]Neilson J R, John G C, Carr J K, et al. Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya [J]. J Virol,1999, 73(5):4393-4403.
[35]Hu DJ, Vanichseni S, Mastro TD, et al. Viral load differences in early infection with two HIV-1 subtypes [J]. AIDS,2001,15(6):683-691.
[36]Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy:a collaborative re-analysis. Collaborative Group on AIDS Incubation and HIV Survival including the CASCADE EU Concerted Action. Concerted Action on SeroConversion to AIDS and Death in Europe [J]. Lancet,2000,355(9210):1131-1137.
[37]Deschamps M M, Fitzgerald D W, Pape J W, et al. HIV infection in Haiti: natural history and disease progression [J]. AIDS,2000,14(16):2515-2521.
[38]Rangsin R, Piyaraj P, Sirisanthana T, et al. The natural history of HIV-1 subtype E infection in young men in Thailand with up to 14 years of follow-up [J]. AIDS, 2007,21 (Suppl 6):S39-S46.
[39]Nelson K E, Costello C, Suriyanon V, et al. Survival of blood donors and their spouses with HIV-1 subtype E (CRF01 A_E) infection in northern Thailand, 1992-2007. AIDS,2007,21(Suppl 6):S47-S54.
[40]Kaleebu P, French N, Mahe C, et al. Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda [J]. J Infect Dis,2002,185(9):1244-1250.
[41]Geretti A M. HIV-1 subtypes:epidemiology and significance for HIV management [J]. Curr Opin Infect Dis,2006,19(1):1-7.
[42]Kwon J A, Yoon S Y, Lee C K, et al. Performance evaluation of three automated human immunodeficiency virus antigen-antibody combination immunoassays [J]. J Virol Methods,2006,133(1):20-26.
[43]Kantor R. Impact of HIV-1 pol diversity on drug resistance and its clinical implications [J]. Curr Opin Infect Dis,2006,19(6):594-606.
[44]Mcmichael A J, Borrow P, Tomaras G D, et al. The immune response during acute HIV-1 infection:clues for vaccine development [J]. Nat Rev Immunol,2010, 10(1):11-23.
[45]Kawashima Y, Pfafferott K, Frater J, et al. Adaptation of HIV-1 to human leukocyte antigen class I [J]. Nature,2009,458(7238):641-645.
[46]Bunnik E M, Euler Z, Welkers M R, et al. Adaptation of HIV-1 envelope gp120 to humoral immunity at a population level [J]. Nat Med,2010,16(9):995-997.
[47]Le Rouzic E, Benichou S. The Vpr protein from HIV-1:distinct roles along the viral life cycle [J]. Retrovirology,2005,2:11.
[48]Lu Y L, Bennett R P, Wills J W, et al. A leucine triplet repeat sequence (LXX)4 in p6gag is important for Vpr incorporation into human immunodeficiency virus type 1 particles [J]. J Virol,1995,69(11):6873-6879.
[49]Tungaturthi P K, Sawaya B E, Singh S P, et al. Role of HIV-1 Vpr in AIDS pathogenesis:relevance and implications of intravirion, intracellular and free Vpr [J]. Biomed Pharmacother,2003,57(1):20-24.
[50]Levy D N, Refaeli Y, Macgregor R R, et al. Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1 [J]. Proc Natl Acad Sci USA,1994,91(23):10873-10877.
[51]Engler A, Stangler T, Willbold D. Structure of human immunodeficiency virus type 1 Vpr(34-51) peptide in micelle containing aqueous solution [J]. Eur J Biochem, 2002,269(13):3264-3269.
[52]Engler A, Stangler T, Willbold D. Solution structure of human immunodeficiency virus type 1 Vpr(13-33) peptide in micelles [J]. Eur J Biochem, 2001,268(2):389-395.
[53]Morellet N, Bouaziz S, Petitjean P, et al. NMR structure of the HIV-1 regulatory protein VPR [J]. J Mol Biol,2003,327(1):215-227.
[54]Bourbigot S, Beltz H, Denis J, et al. The C-terminal domain of the HIV-1 regulatory protein Vpr adopts an antiparallel dimeric structure in solution via its leucine-zipper-like domain [J]. Biochem J,2005,387(Pt 2):333-341.
[55]Mahalingam S, Collman R G, Patel M, et al. Role of the conserved dipeptide Gly75 and Cys76 on HIV-1 Vpr function [J]. Virology,1995,210(2):495-500.
[56]Mahalingam S, Macdonald B, Ugen K E, et al. In vitro and in vivo tumor growth suppression by HIV-1 Vpr [J]. DNA Cell Biol,1997,16(2):137-143.
[57]Singh S P, Tomkowicz B, Lai D, et al. Functional role of residues corresponding to helical domain II (amino acids 35 to 46) of human immunodeficiency virus type 1 Vpr [J]. J Virol,2000,74(22):10650-10657.
[58]Mahalingam S, Khan S A, Murali R, et al. Mutagenesis of the putative alpha-helical domain of the Vpr protein of human immunodeficiency virus type 1: effect on stability and virion incorporation [J]. Proc Natl Acad Sci USA,1995, 92(9):3794-3798.
[59]Mahalingam S, Khan S A, Jabbar M A, et al. Identification of residues in the N-terminal acidic domain of HIV-1 Vpr essential for virion incorporation [J]. Virology,1995,207(1):297-302.
[60]Sherman M P, de Noronha C M, Pearce D, et al. Human immunodeficiency virus type 1 Vpr contains two leucine-rich helices that mediate glucocorticoid receptor coactivation independently of its effects on G(2) cell cycle arrest [J]. J Virol,2000, 74(17):8159-8165.
[61]Nie Z, Bergeron D, Subbramanian R A, et al. The putative alpha helix 2 of human immunodeficiency virus type 1 Vpr contains a determinant which is responsible for the nuclear translocation of proviral DNA in growth-arrested cells [J]. J Virol,1998,72(5):4104-4115.
[62]Subbramanian R A, Yao X J, Dilhuydy H, et al. Human immunodeficiency virus type 1 Vpr localization:nuclear transport of a viral protein modulated by a putative amphipathic helical structure and its relevance to biological activity [J]. J Mol Biol, 1998,278(1):13-30.
[63]Wang B, Ge Y C, Palasanthiran P, et al. Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair:in vivo evolution of vpr quasispecies in blood and plasma [J]. Virology,1996, 223(1):224-232.
[64]Zhou Y, Lu Y, Ratner L. Arginine residues in the C-terminus of HIV-1 Vpr are important for nuclear localization and cell cycle arrest [J]. Virology,1998,242 (2):414-424.
[65]Bourbigot S, Beltz H, Denis J, et al. The C-terminal domain of the HIV-1 regulatory protein Vpr adopts an antiparallel dimeric structure in solution via its leucine-zipper-like domain [J]. Biochem J,2005,387(Pt 2):333-341.
[66]Sawaya B E, Khalili K, Gordon J, et al. Transdominant activity of human immunodeficiency virus type 1 Vpr with a mutation at residue R73 [J]. J Virol,2000, 74(10):4877-4881.
[67]Berglez J M, Castelli L A, Sankovich S A, et al. Residues within the HFRIGC sequence of HIV-1 vpr involved in growth arrest activities [J]. Biochem Biophys Res Commun,1999,264(1):287-290.
[68]Sawaya B E, Khalili K, Gordon J, et al. Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome [J]. J Biol Chem,2000,275(45):35209-35214.
[69]Yao X J, Mouland A J, Subbramanian R A, et al. Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells [J]. J Virol,1998,72(6):4686-4693.
[70]Bischerour J, Tauc P, Leh H, et al. The (52-96) C-terminal domain of Vpr stimulates HIV-1 IN-mediated homologous strand transfer of mini-viral DNA [J]. Nucleic Acids Res,2003,31(10):2694-2702.
[71]Mahalingam S, Patel M, Collman R G, et al. The carboxy-terminal domain is essential for stability and not for virion incorporation of HIV-1 Vpr into virus particles [J]. Virology,1995,214(2):647-652.
[72]Mahalingam S, Macdonald B, Ugen K E, et al. In vitro and in vivo tumor growth suppression by HIV-1 Vpr [J]. DNA Cell Biol,1997,16(2):137-143.
[73]Wang B, Ge Y C, Palasanthiran P, et al. Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair:in vivo evolution of vpr quasispecies in blood and plasma [J]. Virology,1996, 223(1):224-232.
[74]Lum JJ, Cohen OJ, Nie Z, et al. Vpr R77Q is associated with longterm nonprogressive HIV infection and impaired induction of apoptosis [J]. J Clin Invest, 2003,111(10):1547-1554.
[75]Chui C, Cheung P K, Brumme C J, et al. HIV VprR77Q mutation does not influence clinical response of individuals initiating highly active antiretroviral therapy [J]. AIDS Res Hum Retroviruses,2006,22(7):615-618.
[76]Cavert W, Webb C H, Balfour H J. Alterations in the C-terminal region of the HIV-1 accessory gene vpr do not confer clinical advantage to subjects receiving nucleoside antiretroviral therapy [J]. J Infect Dis,2004,189(12):2181-2184.
[77]Cohen A H, Sun N C, Shapshak P, et al. Demonstration of human immunodeficiency virus in renal epithelium in HIV-associated nephropathy [J]. Mod Pathol,1989,2(2):125-128.
[78]Bruggeman L A, Ross M D, Tanji N, et al. Renal epithelium is a previously unrecognized site of HIV-1 infection [J]. J Am Soc Nephrol,2000,11(11): 2079-2087.
[79]Marras D, Bruggeman L A, Gao F, et al. Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy [J]. Nat Med,2002,8(5):522-526.
[80]Dickie P, Roberts A, Uwiera R, et al. Focal glomerulosclerosis in proviral and c-fms transgenic mice links Vpr expression to HIV-associated nephropathy [J]. Virology,2004,322(1):69-81.
[81]Zuo Y, Matsusaka T, Zhong J, et al. HIV-1 genes vpr and nef synergistically damage podocytes, leading to glomerulosclerosis [J]. J Am Soc Nephrol,2006, 17(10):2832-2843.
[82]Conaldi P G, Biancone L, Bottelli A, et al. HIV-1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas upregulation [J]. J Clin Invest,1998,102(12):2041-2049.
[83]Snyder A, Alsauskas Z C, Leventhal J S, et al. HIV-1 viral protein r induces ERK and caspase-8-dependent apoptosis in renal tubular epithelial cells [J]. AIDS,2010, 24(8):1107-1119.
[84]洪韵琳,周德江.临床病理讨论.第96例一发热、咳嗽、进行性呼吸困难[J].中华内科杂志,1986,25(7)：436-439.
[85]Palella F J, Baker R K, Moorman A C, et al. Mortality in the highly active antiretroviral therapy era:changing causes of death and disease in the HIV outpatient study [J]. J Acquir Immune Defic Syndr,2006,43(1):27-34.
[86]刘翌.艾滋病病毒分子亚型流行病学研究进展[J].中国国境卫生检疫杂志,2006,29：146-150.
[87]卓丽,唐小平,陈伟烈,等.广东省艾滋病患者HIV-1基因亚型分析[J].国际流行病学传染病学杂志,2011,38(1)：21-25.
[88]赵飞,王哲,李文杰.河南省1157份人免疫缺陷病毒1型毒株亚型分析[J].中华预防医学杂志,2008,42(6)：418-421.
[89]杨绍敏,李惠琴,陈立力,等.云南省2008-2009年HIV-1病毒株亚型分布[J].中华流行病学杂志,2012,33(8)：836-840.
[90]赵广录,于微,张娟娟,等.深圳地区1992-2008年HIV-1分子流行病学研究[J].中华流行病学杂志,2012,33(1)：82-87.
[91]Jaffe H W, Valdiserri R O, De Cock K M. The reemerging HIV/AIDS epidemic in men who have sex with men [J]. JAMA,2007,298(20):2412-2414.
[92]Tanser F, Barnighausen T, Hund L, et al. Effect of concurrent sexual partnerships on rate of new HIV infections in a high-prevalence, rural South African population:a cohort study [J]. Lancet,2011,378(9787):247-255.
[93]Centers for Disease Control and Prevention (CDC). Prevalence and awareness of HIV infection among men who have sex with men---21 cities, United States,2008. MMWR Morb Mortal Wkly Rep,2010,59(37):1201-1207.
[94]张北川,李秀芳,史同新,等.对中国男同/双性爱者人口数量与艾滋病病毒感染率的初步估测[J].中国性病艾滋病防治,2002,8(4)：197-199.
[95]王岚,王璐,丁正伟,等.中国1995-2009年艾滋病哨点监测主要人群艾滋病病毒感染流行趋势分析[J].中华流行病学杂志,2011,32(1)：20-24.
[96]Lau J T, Lin C, Hao C, et al. Public health challenges of the emerging HIV epidemic among men who have sex with men in China [J]. Public Health,2011, 125(5):260-265.
[97]Zhang X, Wang C, Hengwei W, et al. Risk factors of HIV infection and prevalence of co-infections among men who have sex with men in Beijing, China [J]. AIDS,2007,21(Suppl 8):S53-S57.
[98]Jia M, Luo H, Ma Y, et al. The HIV epidemic in Yunnan Province, China,1989-2007 [J]. J Acquir Immune Defic Syndr,2010,53 (Suppl 1):S34-S40.
[99]Gao F, Robertson D L, Morrison S G, et al. The heterosexual human immunodeficiency virus type 1 epidemic in Thailand is caused by an intersubtype (A/E) recombinant of African origin [J]. J Virol,1996,70(10):7013-7029.
[100]Xiao-Jie Li, Rie Uenishi, Saiki Hase, et al. HIV/AIDS in Asia:The Shape of Epidemics and Their Molecular Epidemiology [J]. Virologica Sinica,2007,22 (6):426-433.
[101]邢辉,潘品良,苏玲,等.1996-1998年中国流行的E亚型艾滋病病毒1型毒株的分子流行病学研究[J].中国性病艾滋病防治,2002,8(4)：200-203.
[102]Wang W, Xu J, Jiang S, et al. The Dynamic Face of HIV-1 Subtypes Among Men who Have Sex with Men in Beijing, China [J]. Curr HIV Res,2011,9(2): 136-139.
[103]Wang W, Jiang S, Li S, et al. Identification of subtype B, multiple circulating recombinant forms and unique recombinants of HIV type 1 in an MSM cohort in China [J]. AIDS Res Hum Retroviruses,2008,24(10):1245-1254.
[104]Zhang X, Li S, Li X, et al. Characterization of HIV-1 subtypes and viral antiretroviral drug resistance in men who have sex with men in Beijing, China [J]. AIDS,2007,21 Suppl 8:S59-S65.
[105]邵一鸣,戴玉林,邢辉.HIV-1和HIV-2混合感染的发现[J].中华实验和临床病毒学杂志,1999,13(4)：383.
[106]Renjifo B, Gilbert P, Chaplin B, et al. Preferential in-utero transmission of HIV-1 subtype C as compared to HIV-1 subtype A or D [J]. AIDS,2004,18(12): 1629-1636.
[107]John-Stewart G C, Nduati R W, Rousseau C M, et al. Subtype C Is associated with increased vaginal shedding of HIV-1 [J]. J Infect Dis,2005,192(3):492-496.
[108]Hudgens M G, Longini I J, Vanichseni S, et al. Subtype-specific transmission probabilities for human immunodeficiency virus type 1 among injecting drug users in Bangkok, Thailand [J]. Am J Epidemiol,2002,155(2):159-168.
[109]Costello C, Nelson K E, Suriyanon V, et al. HIV-1 subtype E progression among northern Thai couples:traditional and non-traditional predictors of survival [J]. Int. J. Epidemiol.,2005,34(3):577-584.
[110]Kaleebu P, French N, Mahe C, et al. Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda [J]. J Infect Dis,2002,185(9):1244-1250.
[111]Baeten J M, Chohan B, Lavreys L, et al. HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads [J]. J Infect Dis,2007,195(8):1177-1180.
[112]Huang W, Eshleman S H, Toma J, et al. Coreceptor tropism in human immunodeficiency virus type 1 subtype D:high prevalence of CXCR4 tropism and heterogeneous composition of viral populations [J]. J Virol,2007,81(15):7885-7893.
[113]Neilson J R, John G C, Carr J K, et al. Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya [J]. J Virol,1999, 73(5):4393-4403.
[114]Fischetti L, Opare-Sem O, Candotti D, et al. Higher viral load may explain the dominance of CRF02_AG in the molecular epidemiology of HIV in Ghana [J]. AIDS, 2004,18(8):1208-1210.
[115]Hu D J, Vanichseni S, Mastro T D, et al. Viral load differences in early infection with two HIV-1 subtypes [J]. AIDS,2001,15(6):683-691.
[116]Peters PJ, Moore DM, Mermin J, et al. Antiretroviral therapy improves renal function among HIV-infected Ugandans [J]. Kidney Int.,2008,74(7):925-929.
[117]Alexander C S, Montessori V, Wynhoven B, et al. Prevalence and response to antiretroviral therapy of non-B subtypes of HIV in antiretroviral-naive individuals in British Columbia [J]. Antivir Ther,2002,7(1):31-35.
[118]Bocket L, Cheret A, Deuffic-Burban S, et al. Impact of human immunodeficiency virus type 1 subtype on first-line antiretroviral therapy effectiveness [J]. Antivir Ther,2005,10(2):247-254.
[119]Atlas A, Granath F, Lindstrom A, et al. Impact of HIV type 1 genetic subtype on the outcome of antiretroviral therapy [J]. AIDS Res Hum Retroviruses,2005, 21(3):221-227.
[120]Fischer A, Lejczak C, Lambert C, et al. Is the Vpr R77Q mutation associated with long-term non-progression of HIV infection? [J]. AIDS,2004,18(9):1346-1347.
[121]Mologni D, Citterio P, Menzaghi B, et al. Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients [J]. AIDS,2006,20(4):567-574.
[122]Brenner C, Kroemer G. The mitochondriotoxic domain of Vpr determines HIV-1 virulence [J]. J Clin Invest,2003,111(10):1455-1457.
[123]Jacotot E, Ravagnan L, Loeffler M, et al. The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore [J]. J Exp Med,2000,191(1):33-46.
[124]Gaynor E M, Chen I S. Analysis of apoptosis induced by HIV-1 Vpr and examination of the possible role of the hHR23A protein [J]. Exp Cell Res,2001, 267(2):243-257.
[125]Rodes B, Toro C, Paxinos E, et al. Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection [J]. AIDS,2004,18(8):1109-1116.
[126]Green DR, Kroemer G. The pathophysiology of mitochondrial cell death [J]. Science,2004,305(5684):626-629.
[127]Jian H, Zhao L J. Pro-apoptotic activity of HIV-1 auxiliary regulatory protein Vpr is subtype-dependent and potently enhanced by nonconservative changes of the leucine residue at position 64 [J]. J Biol Chem,2003,278(45):44326-44330.
[128]Cartas M, Singh S P, Serio D, et al. Intravirion display of a peptide corresponding to the dimer structure of protease attenuates HIV-1 replication [J]. DNA Cell Biol,2001,20(12):797-805.
[1]Yuan X, Matsuda Z, Matsuda M, et al. Human immunodeficiency virus vpr gene encodes a virion-associated protein [J]. AIDS Res Hum Retroviruses,1990, 6(11):1265-1271.
[2]Cohen EA, Terwilliger EF, Jalinoos Y, et al. Identification of HIV-1 vpr product and function [J]. J Acquir Immune Defic Syndr,1990,3(1):11-18.
[3]Planelles V, Jowett JB, Li QX, et al. Vpr-induced cell cycle arrest is conserved among primate lentiviruses [J]. J Virol,1996,70(4):2516-2524.
[4]Emerman M. HIV-1, Vpr and the cell cycle. Curr Biol 1996,6(9):1096-1103.
[5]Feldherr CM, Feldherr AB. The nuclear membrane as a barrier to the free diffusion of proteins [J]. Nature,1960,185:250-251.
[6]Lewis PF, Emerman M. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus [J]. J Virol,1994,68(1):510-516.
[7]Bukrinsky MI, Sharova N, Dempsey MP, et al. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes [J]. Proc Natl Acad Sci USA, 1992,89(14):6580-6584.
[8]Lu YL, Spearman P, Ratner L. Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions [J]. J Virol,1993, 67(11):6542-6550.
[9]Di Marzio P, Choe S, Ebright M, et al. Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr [J]. J Virol,1995,69(12):7909-7916.
[10]Gallay P, Hope T, Chin D, et al. HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway [J]. Proc Natl Acad Sci USA,1997,94(18):9825-9830.
[11]Dismuke DJ, Aiken C. Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex [J]. J Virol,2006,80(8):3712-3720.
[12]Gorlich D. Nuclear protein import [J]. Curr Opin Cell Biol 1997,9(3):412-419.
[13]Herold A, Truant R, Wiegand H, et al. Determination of the functional domain organization of the importin alpha nuclear import factor [J]. J Cell Biol,1998, 143(2):309-318.
[14]Kobe B. Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha [J]. Nat Struct Biol,1999, 6(4):388-397.
[15]Moore MS, Blobel G. The GTP-binding protein Ran/TC4 is required for protein import into the nucleus [J]. Nature,1993,365(6447):661-663.
[16]Melchior F, Paschal B, Evans J, et al. Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential transport factor [J]. J Cell Biol,1993,123(6 Pt 2):1649-1659.
[17]Paschal BM, Gerace L. Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62 [J]. J Cell Biol,1995, 129(4):925-937.
[18]Kotera I, Sekimoto T, Miyamoto Y, et al. Importin alpha transports CaMKIV to the nucleus without utilizing importin beta [J]. Embo J,2005,24(5):942-951.
[19]Takizawa CG, Weis K, Morgan DO. Ran-independent nuclear import of cyclin B1-Cdc2 by importin beta [J]. Proc Natl Acad Sci USA,1999,96(14):7938-7943.
[20]Siomi H, Dreyfuss G. A nuclear localization domain in the hnRNP A1 protein [J]. J Cell Biol,1995,129(3):551-560.
[21]Michael WM, Choi M, Dreyfuss G. A nuclear export signal in hnRNP Al:a signal-mediated, temperature-dependent nuclear protein export pathway [J]. Cell, 1995,83(3):415-422.
[22]Aitchison JD, Blobel G, Rout MP. Kap104p:a karyopherin involved in the nuclear transport of messenger RNA binding proteins [J]. Science,1996, 274(5287):624-627.
[23]Nakielny S, Siomi MC, Siomi H, et al. Transportin:nuclear transport receptor of a novel nuclear protein import pathway [J]. Exp Cell Res,1996,229(2):261-266.
[24]Jenkins Y, McEntee M, Weis K, et al. Characterization of HIV-1 vpr nuclear import:analysis of signals and pathways [J]. J Cell Biol,1998,143(4):875-885.
[25]Efthymiadis A, Shao H, Hubner S, et al. Kinetic characterization of the human retinoblastoma protein bipartite nuclear localization sequence (NLS) in vivo and in vitro. A comparison with the SV40 large T-antigen NLS [J]. J Biol Chem,1997, 272(35):22134-22139.
[26]Jans DA, Jans P, Julich T, et al. Intranuclear binding by the HIV-1 regulatory protein VPR is dependent on cytosolic factors [J]. Biochem Biophys Res Commun, 2000,270(3):1055-1062.
[27]Nitahara-Kasahara Y, Kamata M, Yamamoto T, et al. Novel nuclear import of Vpr promoted by importin alpha is crucial for human immunodeficiency virus type 1 replication in macrophages [J]. J Virol,2007,81(10):5284-5293.
[28]Kamata M, Nitahara-Kasahara Y, Miyamoto Y, et al. Importinalpha promotes passage through the nuclear pore complex of human immunodeficiency virus type 1 Vpr [J]. J Virol,2005,79(6):3557-3564.
[29]Connor RI, Chen BK, Choe S, et al. Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes [J]. Virology, 1995,206(2):935-944.
[30]Blomer U, Naldini L, Kafri T, et al. Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector [J]. J Virol,1997,71(9):6641-6649.
[31]Jacquot G, Le Rouzic E, David A,et al. Localization of HIV-1 Vpr to the nuclear envelope:impact on Vpr functions and virus replication in macrophages [J]. Retrovirology,2007,4:84.
[32]Caly L, Saksena NK, Piller SC, et al. Impaired nuclear import and viral incorporation of Vpr derived from a HIV long-term non-progressor [J]. Retrovirology, 2008,5:67.
[33]Popov S, Rexach M, Ratner L, et al. Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex [J]. J Biol Chem,1998, 273(21):13347-13352.
[34]Keele BF, Giorgi EE, Salazar-Gonzalez JF, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection [J]. Proc Natl Acad Sci USA,2008,105(21):7552-7557.
[35]Fischer W, Ganusov VV, Giorgi EE, et al. Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing [J]. PLoS One,2010,5(8):e12303.
[36]Iijima S, Nitahara-Kasahara Y, Kimata K, et al. Nuclear localization of Vpr is crucial for the efficient replication of HIV-1 in primary CD4+T cells [J]. Virology, 2004,327(2):249-261.
[37]Yamashita M, Perez O, Hope TJ, et al. Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells [J]. PLoS Pathog 2007, 3(10):1502-1510.
[38]Morellet N, Bouaziz S, Petitjean P, et al. NMR structure of the HIV-1 regulatory protein VPR [J]. J Mol Biol,2003,327(1):215-227.
[39]Singh SP, Tomkowicz B, Lai D, et al. Functional role of residues corresponding to helical domain II (amino acids 35 to 46) of human immunodeficiency virus type 1 Vpr [J]. J Virol,2000,74(22):10650-10657.
[40]Mahalingam S, Ayyavoo V, Patel M, et al. Nuclear import, virion incorporation, and cell cycle arrest/differentiation are mediated by distinct functional domains of human immunodeficiency virus type 1 Vpr [J]. J Virol,1997,71(9):6339-6347.
[41]Fritz JV, Didier P, Clamme JP, et al. Direct Vpr-Vpr interaction in cells monitored by two photon fluorescence correlation spectroscopy and fluorescence lifetime imaging [J]. Retrovirology,2008,5:87.
[42]Agostini I, Popov S, Li J, et al. Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import of the viral preintegration complex [J]. Exp Cell Res, 2000,259(2):398-403.
[43]Kamata M, Aida Y. Two putative alpha-helical domains of human immunodeficiency virus type 1 Vpr mediate nuclear localization by at least two mechanisms [J]. J Virol,2000,74(15):7179-7186.
[44]Le Rouzic E, Mousnier A, Rustum C, et al. Docking of HIV-1 Vpr to the nuclear envelope is mediated by the interaction with the nucleoporin hCGl. J Biol Chem, 2002,277(47):45091-45098.
[45]Fouchier RA, Meyer BE, Simon JH, et al. Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex [J]. J Virol, 1998,72(7):6004-6013.
[46]Vodicka MA, Koepp DM, Silver PA,et al. HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection [J]. Genes Dev,1998, 12(2):175-185.
[47]Rexach M, Blobel G. Protein import into nuclei:association and dissociation reactions involving transport substrate, transport factors, and nucleoporins [J]. Cell, 1995,83(5):683-692.
[48]Kutay U, Izaurralde E, Bischoff FR, et al. Dominant-negative mutants of importin-beta block multiple pathways of import and export through the nuclear pore complex [J]. Embo J,1997,16(6):1153-1163.
[49]Karni O, Friedler A, Zakai N, et al. A peptide derived from the N-terminal region of HIV-1 Vpr promotes nuclear import in permeabilized cells:elucidation of the NLS region of the Vpr [J]. FEBS Lett,1998,429(3):421-425.
[50]Zhou Y, Lu Y, Ratner L. Arginine residues in the C-terminus of HIV-1 Vpr are important for nuclear localization and cell cycle arrest [J]. Virology,1998, 242(2):414-424.
[51]Levy DN, Refaeli Y, Weiner DB. Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency [J]. J Virol,1995,69(2):1243-1252.
[52]Wang L, Mukherjee S, Jia F, et al. Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Spl and trans-activation of viral long terminal repeat [J]. J Biol Chem,1995,270(43): 25564-25569.
[53]McAllister JJ, Phillips D, Millhouse S, et al. Analysis of the HIV-1 LTR NF-kappaB-proximal Sp site Ⅲ:evidence for cell type-specific gene regulation and viral replication [J]. Virology,2000,274(2):262-277.
[54]Vanitharani R, Mahalingam S, Rafaeli Y, et al. HIV-1 Vpr transactivates LTR-directed expression through sequences present within -278 to-176 and increases virus replication in vitro [J]. Virology,2001,289(2):334-342.
[55]Agostini I, Navarro JM, Rey F, et al. The human immunodeficiency virus type 1 Vpr transactivator:cooperation with promoter-bound activator domains and binding to TFIIB [J]. J Mol Biol,1996,261(5):599-606.
[56]Felzien LK, Woffendin C, Hottiger MO, et al. HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator [J]. Proc Natl Acad Sci USA 1998,95(9):5281-5286.
[57]Sawaya BE, Khalili K, Rappaport J, et al. Suppression of HIV-1 transcription and replication by a Vpr mutant [J]. Gene Ther,1999,6(5):947-950.
[58]Sawaya BE, Khalili K, Gordon J, et al. Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome [J]. J Biol Chem,2000,275(45):35209-35214.
[59]Refaeli Y, Levy DN, Weiner DB. The glucocorticoid receptor type Ⅱ complex is a target of the HIV-1 vpr gene product [J]. Proc Natl Acad Sci USA,1995,92(8): 3621-3625.
[60]Kino T, Gragerov A, Kopp JB, et al. The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor [J]. J Exp Med,1999,189(1):51-62.
[61]Sherman MP, de Noronha CM, Pearce D, et al. Human immunodeficiency virus type 1 Vpr contains two leucine-rich helices that mediate glucocorticoid receptor coactivation independently of its effects on G(2) cell cycle arrest [J]. J Virol,2000, 74(17):8159-8165.
[62]Kino T, Gragerov A, Slobodskaya O, et al. Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces transcription of the HIV-1 and glucocorticoid-responsive promoters by binding directly to p300/CBP coactivators [J]. J Virol,2002,76(19):9724-9734.
[63]Muthumani K, Choo AY, Zong WX, et al. The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1 [J]. Nat Cell Biol,2006,8(2):170-179.
[64]Chatterton RT Jr, Green D, Harris S, et al. Longitudinal study of adrenal steroids in a cohort of HIV-infected patients with hemophilia [J]. J Lab Clin Med,1996, 127(6):545-552.
[65]Russo FO, Patel PC, Ventura AM, et al. HIV-1 long terminal repeat modulation by glucocorticoids in monocytic and lymphocytic cell lines [J]. Virus Res,1999, 64(1):87-94.
[66]Kino T, Kopp JB, Chrousos GP. Glucocorticoids suppress human immunodeficiency virus type-1 long terminal repeat activity in a cell type-specific, glucocorticoid receptor-mediated fashion:direct protective effects at variance with clinical phenomenology [J]. J Steroid Biochem Mol Biol,2000,75:283-290.
[67]Laurence J, Sellers MB, Sikder SK. Effect of glucocorticoids on chronic human immunodeficiency virus (HIV) infection and HIV promoter mediated transcription [J]. Blood,1989,74(1):291-297.
[68]Kinter AL, Biswas P, Alfano M, et al. Interleukin-6 and glucocorticoids synergistically induce human immunodeficiency virus type-1 expression in chronically infected U1 cells by a long terminal repeat independent post-transcriptional mechanism [J]. Mol Med,2001,7:668-678.
[69]Hoshino S, Konishi M, Mori M, et al. HIV-1 Vpr induces TLR4/MyD88-mediated IL-6 production and reactivates viral production from latency [J]. J Leukoc Biol,2010,87(6):1133-1143.
[70]Bressler P, Poli G, Justement JS, et al. Glucocorticoids synergize with tumor necrosis factor alpha in the induction of HIV expression from a chronically infected promonocytic cell line [J]. AIDS Res Hum Retroviruses,1993,9(6):547-551.
[71]Schafer EA, Venkatachari NJ, Ayyavoo V. Antiviral effects of mifepristone on human immunodeficiency virus type-1 (HIV-1):targeting Vpr and its cellular partner, the glucocorticoid receptor (GR) [J]. Antiviral Res,2006,72(3):224-232.
[72]Wiegers K, Schwarck D, Reimer R, et al. Activation of the glucocorticoid receptor releases unstimulated PBMCs from an early block in HIV-1 replication [J]. Virology,2008,375(1):73-84.
[73]Fletcher TM, Brichacek B, Sharova N, et al. Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIV(SM) [J]. Embo J,1996,15(22):6155-6165.
[74]Subbramanian RA, Kessous-Elbaz A, Lodge R, et al. Human immunodeficiency virus type 1 Vpr is a positive regulator of viral transcription and infectivity in primary human macrophages [J]. J Exp Med,1998,187(7):1103-1111.
[75]Wen X, Duus KM, Friedrich TD, et al. The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4Acontaining ubiquitin ligase complex using VprBP/DCAF1 as an adaptor [J]. J Biol Chem,2007,282(37):27046-27057.
[76]DeHart JL, Zimmerman ES, Ardon O, et al. HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system [J]. Virol J, 2007,4:57.
[77]Zhao LJ, Mukherjee S, Narayan O. Biochemical mechanism of HIV-I Vpr function Specific interaction with a cellular protein [J]. J Biol Chem,1994,269(22): 15577-15582.
[78]Casey L, Wen X, de Noronha CM:The functions of the HIV1 protein Vpr and its action through the DCAF1.DDB1.Cullin4 ubiquitin ligase [J]. Cytokine,2010,51(1): 1-9.
[79]Zimmerman E, Sherman M, Blackett J, et al. Human immunodeficiency virus type 1 Vpr induces DNA replication stress in vitro and in vivo [J]. J Virol,2006, 80(21):10407-10418.
[80]Goh WC, Rogel ME, Kinsey CM, et al. HIV-1 Vpr increases viral expression by manipulation of the cell cycle:a mechanism for selection of Vpr in vivo [J]. Nat Med, 1998,4(1):65-71.
[81]Igarashi T, Brown CR, Endo Y, et al. Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans [J]. Proc Natl Acad Sci USA,2001, 98(2):658-663.
[82]Bergamaschi A, Ayinde D, David A, et al. The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection [J]. J Virol,2009,83(10):4854-4860.
[83]Cosenza MA, Zhao ML, Lee SC. HIV-1 expression protects macrophages and microglia from apoptotic death [J]. Neuropathol Appl Neurobiol,2004,30(5):478-490.
[84]Fernandez Larrosa PN, Croci DO, Riva DA, et al. Apoptosis resistance in HIV-1 persistently-infected cells is independent of active viral replication and involves modulation of the apoptotic mitochondrial pathway [J]. Retrovirology,2008,5:19.
[85]Fukumori T, Akari H, Yoshida A, et al. Regulation of cell cycle and apoptosis by human immunodeficiency virus type 1 Vpr [J]. Microbes Infect,2000,2(9):1011-1017.
[86]Conti L, Rainaldi G, Matarrese P, et al. The HIV-1 vpr protein acts as a negative regulator of apoptosis in a human lymphoblastoid T cell line:possible implications for the pathogenesis of AIDS [J]. J Exp Med,1998,187(3):403-413.
[87]Rostad SW, Sumi SM, Shaw CM, et al. Human immunodeficiency virus (HIV) infection in brains with AIDS-related leukoencephalopathy [J]. AIDS Res Hum Retroviruses,1987,3(4):363-373.
[88]McArthur JC. HIV dementia:an evolving disease [J]. J Neuroimmunol,2004, 157(1-2):3-10.
[89]Porwit A, Parravicini C, Petren AL, et al. Cell association of HIV in AIDS-related encephalopathy and dementia [J]. Apmis,1989,97(1):79-90.
[90]Williams KC, Corey S, Westmoreland SV, et al. Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques:implications for the neuropathogenesis of AIDS [J]. J Exp Med, 2001,193(8):905-915.
[91]Glass JD, Fedor H, Wesselingh SL, et al. Immunocytochemical quantitation of human immunodeficiency virus in the brain:correlations with dementia [J]. Ann Neurol,1995,38(5):755-762.
[92]Fischer-Smith T, Tedaldi EM, Rappaport J. CD163/CD16 coexpression by circulating monocytes/macrophages in HIV:potential biomarkers for HIV infection and AIDS progression [J]. AIDS Res Hum Retroviruses,2008,24(3):417-421.
[93]Fischer-Smith T, Croul S, Sverstiuk AE, et al. CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia:perivascular accumulation and reservoir of HIV infection [J]. J Neurovirol,2001,7(6):528-541.
[94]Fischer-Smith T, Rappaport J. Evolving paradigms in the pathogenesis of HIV-1-associated dementia [J]. Expert Rev Mol Med,2005,7(27):1-26.
[95]Wheeler ED, Achim CL, Ayyavoo V. Immunodetection of human immunodeficiency virus type 1 (HIV-1) Vpr in brain tissue of HIV-1 encephalitic patients [J]. J Neurovirol,2006,12(3):200-210.
[96]Jones GJ, Barsby NL, Cohen EA, et al. HIV-1 Vpr causes neuronal apoptosis and in vivo neurodegeneration [J]. J Neurosci,2007,27(14):3703-3711.
[97]Sabbah EN, Roques BP. Critical implication of the (70-96) domain of human immunodeficiency virus type 1 Vpr protein in apoptosis of primary rat cortical and striatal neurons [J]. J Neurovirol,2005,11(6):489-502.
[98]Patel CA, Mukhtar M, Pomerantz RJ. Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cells [J]. J Virol,2000,74(20):9717-9726.
[99]Acheampong E, Mukhtar M, Parveen Z, et al. Ethanol strongly potentiates apoptosis induced by HIV-1 proteins in primary human brain microvascular endothelial cells [J]. Virology,2002,304(2):222-234.
[100]Rom I, Deshmane SL, Mukerjee R, et al. HIV-1 Vpr deregulates calcium secretion in neural cells [J]. Brain Res,2009,1275:81-86.
[101]Hogan TH, Nonnemacher MR, Krebs FC, et al. HIV-1 Vpr binding to HIV-1 LTR C/EBP cis-acting elements and adjacent regions is sequence-specific [J]. Biomed Pharmacother,2003,57(1):41-48.
[102]Burdo TH, Nonnemacher M, Irish BP, et al. High-affinity interaction between HIV-1 Vpr and specific sequences that span the C/EBP and adjacent NF-kappaB sites within the HIV-1 LTR correlate with HIV-1-associated dementia [J]. DNA Cell Biol, 2004,23(4):261-269.
[103]Kilareski EM, Shah S, Nonnemacher MR, et al. Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage [J]. Retrovirology,2009, 6:118.
[104]Wyatt CM, Rosenstiel PE, Klotman PE. HIV-associated nephropathy [J]. Contrib Nephrol,2008,159:151-161.
[105]Kopp J, Smith M, Nelson G, et al. MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis [J]. Nat Genet,2008,40(10):1175-1184.
[106]Tang P, Jerebtsova M, Przygodzki R, et al. Fibroblast growth factor-2 increases the renal recruitment and attachment of HIV-infected mononuclear cells to renal tubular epithelial cells [J]. Pediatr Nephrol,2005,20(12):1708-1716.
[107]Dickie P, Roberts A, Uwiera R, et al. Focal glomerulosclerosis in proviral and c-frms transgenic mice links Vpr expression to HIV-associated nephropathy [J]. Virology,2004,322(1):69-81.
[108]Zhong J, Zuo Y, Ma J, et al. Expression of HIV-1 genes in podocytes alone can lead to the full spectrum of HIV-1-associated nephropathy [J]. Kidney Int,2005, 68(3):1048-1060.
[109]Muthumani K, Bagarazzi M, Conway D, et al. Inclusion of Vpr accessory gene in a plasmid vaccine cocktail markedly reduces Nef vaccine effectiveness in vivo resulting in CD4 cell loss and increased viral loads in rhesus macaques [J]. J Med Primatol,2002,31(4-5):179-185.
[110]Moon HS, Yang JS. Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells [J]. Mol Cells,2006,21(1):7-20.
[111]Azad AA. Could Nef and Vpr proteins contribute to disease progression by promoting depletion of bystander cells and prolonged survival of HIV-infected cells? [J] Biochem Biophys Res Commun,2000,267(3):677-685.
[112]Yasuda J, Miyao T, Kamata M, et al. T cell apoptosis causes peripheral T cell depletion in mice transgenic for the HIV-1 vpr gene [J]. Virology,2001,285(2): 181-192.
[113]Li G, Park HU, Liang D, et al. Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R [J]. Retrovirology,2010,7:59.
[114]Muthumani K, Zhang D, Hwang DS, et al. Adenovirus encoding HIV-1 Vpr activates caspase 9 and induces apoptotic cell death in both p53 positive and negative human tumor cell lines [J]. Oncogene,2002,21(30):4613-4625.
[115]Majumder B, Venkatachari NJ, Schafer EA, et al. Dendritic cells infected with vpr-positive human immunodeficiency virus type 1 induce CD8+T-cell apoptosis via upregulation of tumor necrosis factor alpha [J]. J Virol,2007,81(14):7388-7399.
[116]Richard J, Sindhu S, Pham TN, et al. HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell-mediated killing [J]. Blood,2010,115(7):1354-1363.
[117]Majumder B, Venkatachari NJ, O'Leary S, et al. Infection with Vprpositive mhuman immunodeficiency virus type 1 impairs NK cell function indirectly through cytokine dysregulation of infected target cells [J]. J Virol,2008,82(14):7189-7200.
[118]Majumder B, Janket ML, Schafer EA, et al. Human immunodeficiency virus type 1 Vpr impairs dendritic cell maturation and T-cell activation:implications for viral immune escape [J]. J Virol,2005,79(13):7990-8003.
[119]Venkatachari NJ, Majumder B, Ayyavoo V. Human immunodeficiency virus (HIV) type 1 Vpr induces differential regulation of T cell costimulatory molecules: direct effect of Vpr on T cell activation and immune function [J]. Virology,2007, 358(2):347-356.
[120]Lang SM, Weeger M, Stahl-Hennig C, et al. Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus [J]. J Virol,1993,67(2):902-912.
[121]Tzitzivacos DB, Tiemessen CT, Stevens WS, et al. Viral genetic determinants of nonprogressive HIV type 1 subtype C infection in antiretroviral drug-naive children [J]. AIDS Res Hum Retroviruses,2009,25(11):1141-1148.
[122]Aquaro S, Svicher V, Schols D, et al. Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages:new therapeutic strategies [J]. J Leukoc Biol,2006,80(5):1103-1110.
[123]Dutta T, Agashe HB, Garg M, et al. Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro [J]. J Drug Target,2007,15(1):89-98.
[124]Swingler S, Mann AM, Zhou J, et al. Apoptotic killing of HIV-1-infected macrophages is subverted by the viral envelope glycoprotein [J]. PLoS Pathog,2007, 3(9):1281-1290.
[125]Kapasi AA, Coscia SA, Pandya MP, et al. Morphine modulates HIV-1 gp160-induced murine macrophage and human monocyte apoptosis by disparate ways [J]. J Neuroimmunol,2004,148(1-2):86-96.
[126]Li G, Bukrinsky M, Zhao RY. HIV-1 viral protein R (Vpr) and its interactions with host cell [J]. Curr HIV Res,2009,7(2):178-183.
[127]Liang D, Benko Z, Agbottah E, et al. Anti-vpr activities of heat shock protein 27 [J]. Mol Med,2007,13(5-6):229-239.
[128]Iordanskiy S, Zhao Y, Dubrovsky L, et al. Heat shock protein 70 protects cells from cell cycle arrest and apoptosis induced by human immunodeficiency virus type 1 viral protein R [J]. J Virol,2004,78(18):9697-9704.
[129]Yedavalli VS, Shih HM, Chiang YP, et al. Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1 [J]. J Virol,2005, 79:13735-13746.
[130]Gibellini D, Re MC, Ponti C, et al. HIV-1 Tat protein concomitantly down-regulates apical caspase-10 and up-regulates c-FLIP in lymphoid T cells:a potential molecular mechanism to escape TRAIL cytotoxicity [J]. J Cell Physiol,2005, 203(3):547-556.
[131]Haffar OK, Smithgall MD, Popov S, et al. CNI-H0294, a nuclear importation inhibitor of the human immunodeficiency virus type 1 genome, abrogates virus replication in infected activated peripheral blood mononuclear cells [J]. Antimicrob Agents Chemother,1998,42:1133-1138.
[132]Paxton W, Connor RI, Landau NR. Incorporation of Vpr into human immunodeficiency virus type 1 virions:requirement for the p6 region of gag and mutational analysis [J]. J Virol,1993,67(12):7229-7237.
[133]Ao Z, Yu Z, Wang L, et al. Vprl4-88-Apobec3G fusion protein is efficiently incorporated into Vif-positive HIV-1 particles and inhibits viral infection [J]. PLoS ONE,2008,3(4):e1995.
[134]Mariani R, Chen D, Schrofelbauer B, et al. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif [J]. Cell,2003,114:21-31.
[135]Stewart SA, Poon B, Jowett JB, et al. Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells [J]. Proc Natl Acad Sci USA,1999,96(21): 12039-12043.
[136]Ayyavoo V, Mahboubi A, Mahalingam S, et al. HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B [J]. Nat Med, 1997,3(10):1117-1123.
[137]Shimura M, Tanaka Y, Nakamura S, et al. Micronuclei formation and aneuploidy induced by Vpr, an accessory gene of human immunodeficiency virus type 1 [J]. Faseb J,1999,13(6):621-637.