人流感病毒（H3N2）鼠肺模型适应性及银翘散抑制病毒复制作用研究
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摘要
目的：
1.研究人甲型H3N2流感病毒Aichi株(A/Aichi/2/68, H3N2)在BALB/c小鼠肺-肺模型上的适应过程。
2.制备银翘散水煎剂冻干样品并进行含量控制,为探讨银翘散抑制流感病毒机理提供物质基础。
3.考察银翘散样品体外抗甲型流感病毒H3N2的作用,比较细胞病变抑制法和空斑减少试验不同适用条件。
4.探讨银翘散样品体内抑制甲型流感病毒H3N2复制作用及途径。
方法：
1.以人类流感病毒株A/Aichi/2/68(H3N2)鼠肺-肺连续传代6次建立鼠肺适应株,比较每代适应株小鼠生存状态、肺指数、病毒滴度及血凝效价的改变,取第0、第6代鼠肺悬液进行NS1蛋白测序,找到野生株转变为适应株的突变氨基酸,探明突变发生过程中的关键事件。
2.采用高效液相色谱法分别测定银翘散中3味中药金银花、牛蒡子、甘草酸中绿原酸、牛蒡子苷、甘草酸含量,对自制银翘散水煎剂冻干样品进行质量控制。
3.细胞培养测定抗病毒效果。以细胞病变抑制法和空斑减少试验法,在不同试验策略(治疗、保护)下,评价银翘散体外抗流感病毒H3N2作用,比较2种方法不同适用条件。
4.H3N2鼠肺适应株滴鼻感染BALB/c小鼠,观察生存状态及检测肺指数；以苏木素-伊红染色(HE染色)法观察病理改变；透射电镜观察肺泡超微结构改变及病毒感染情况；将鼠肺悬液以空斑减少试验定量检测感染性病毒滴度,蛋白免疫印迹技术(western blot, WB)检测核蛋白(nucleoprotein, NP)表达。
结果：
1.第1代-第2代小鼠生存状态、鼠肺大体病变、肺指数、病毒滴度及血凝效价结果与正常对照组相比,差异无统计学意义(P>0.05)；第3代-第4代小鼠肺指数、病毒滴度及血凝效价逐渐升高；第5代、第6代小鼠出现耸毛,蜷缩,少食,少动,呼吸急促,进食、饮水量骤减,体重减轻等明显感染症状,鼠肺出现逐渐加重的水肿、淤血,呈肺肝样变,肺指数、病毒滴度、血凝效价结果与正常对照组比较,差异显著(P<0.01)；第6代鼠肺适应株NS1蛋白125位甘氨酸突变为天冬氨酸。
2.银翘散水煎剂冻干样品质控系统具有良好的稳定性和可重复性,受试样品中绿原酸、牛蒡子苷、甘草酸的含量符合现行药典标准。
3.体外抑制实验中,4～32mg/mL银翘散样品在治疗及保护模式下,均有较好的抑制病毒、提高细胞存活率的作用(P<0.01)；空斑减少试验结果显示4mg/mL银翘散样品两种模式SI分别为39.31及43.48,能有效抑制流感病毒,符合CPE的结果。
4.体内实验结果显示,银翘散大剂量(5g/kg)可以减轻全身症状,降低肺指数;改善鼠肺病变,范围<50%;减少肺泡腔渗出物、肺泡微细结构改变及病毒颗粒数量;降低鼠肺病毒滴度及鼠肺流感病毒核蛋白表达量,与模型对照组比较,差异具有统计学意义(P<0.05)。
结论：
1.该适应株模型提供了一个了解甲型流感病毒跨物种适应性的研究工具,不仅阐述了野生型流感病毒株在新宿主上产生适应性的过程,为探索适应过程中的病毒与宿主的分子变化打下基础,也为后续药理研究建立了平台,对于评价药物对H3N2流感病毒治疗效果及其作用机制具有重要意义。
2.银翘散冻干样品可以有效保护水煎液中有效成分,与传统剂型相比,易于标准定量,操控性强,适合进行药理及作用机制研究。
4.银翘散样品体外有抗甲型流感病毒H3N2的作用；MTT法适用于抗病毒药物初步筛选,而空斑减少试验适用于精确测定药物抗病毒活性。
5.银翘散样品体内有抑制甲1型流感病毒H3N2复制的作用,主要作用于病毒复制早期抑制NP蛋白合成过程中。
Objective:
1. Observe the adaptation process of Influenza A H3N2influenza virus (A/Aichi/2/68, H3N2) on BALB/c mouse lung model.
2. Establish a control method of Yinqiao powder freeze-dried sample, provide the material basis to explore the mechanism of inhibition of influenza virus by Yinqiao powder.
3. Inspect the antiviral effect of Yinqiao powder in vitro.
4. Explore the inhibition of viral replication by Yinqiao powder in vivo.
Methods:
1. The human influenza virus strains A/Aichi/2/68A (H3N2) as a research object, compared with survival status of mouse, pulmonary index, the virus titer and the hemagglutination titer of each generation, to find the changes of adaption strains between the wild strain and the mutation strain.
2. High performance liquid chromatography (HPLC) was used to determinate the quality of the honeysuckle, Arctium, glycyrrhizic acid.
3. Determined the antiviral effect by cell culture. Evaluated potency inhibition by the cytopathic effect (CPE) and the plaque reduction test method under different experimental strategies (treatment, protection)
4. We use BALB/c mice which were intranasal inoculated with H3N2strain of influenza A virus, to observe the living conditions, determinate lung index, to observed pathological changes by hematoxylin-eosin staining (HE staining), the alveolar ultrastructure changes by transmission electron microscopy; the mouse lung suspension were detected the quantity of infectious virus titer by reduced plaque test and the nucleoprotein (NP) expression by Western blot.
Results:
1. In the passage process of the mouse lung, the HA of human influenza virus H3N2changes to adapt to the new mouse host, with the125amino acid point of NS1protein mutations, the strain have more replication capacity, along with the viral titer increased, the mice began to appear towering hair, curled up, diet reduced, lack of exercise, shortness of breath, eating and drinking plummeted, weight loss and other symptoms of infection, mouse lungs emerge more and more severe edema, congestion and lung hepatization.
2. The quality control system of Yinqiao powder freeze-dried samples has good stability and repeatability, the chlorogenic acid, arctiin and licorice ammonium of this sample met the required of the national pharmacopoeia.
3. In vitro inhibition experiments, various concentrations of Yinqiao powder samples had better suppress the virus and cell survival effect (P<0.01) in the mode of treatment and protection; plaque reduction test results show that SI of two modes were39.31and43.48respectively, can effectively inhibit influenza virus, in line with the results of the CPE.
4. In vivo experimental results show that the Yinqiaosan sample can reduce the systemic symptoms, lung index, the scope of the rat lung lesions, alveolar space exudate, alveolar ultrastructure change and virus particle number; reduce mouse lung virus titers and mouse lung expression of nucleoprotein (nucleoprotein, NP).
Conclusion:
1. The adapted strains model provides an research tool to understanding the adaption of type A influenza virus cross-species, not only described the probably rocess of wild-type influenza virus strains in the new host adaptation, lay groundwork to explore the virus and its host the molecular changes in the process of adaptation, but also establish a platform for subsequent pharmacological studies, it has great significance for the evaluation antiviral effect and mechanism of drug treatment on H3N2influenza virus.
2. Yinqiao powder freeze-dried samples can effectively protect the active ingredient in the decoction, and compared to conventional formulations, get more easier standard quantitative, handling more suitable for the pharmacology and mechanism studies.
3. Yinqiao powder samples has anti-influenza A H3N2virus effect in vitro.
4. Yinqiao powder sample has inhibit replication of A type influenza virus H3N2in vivo, the major role is at the process of viral replication.
1.研究人甲型H3N2流感病毒Aichi株(A/Aichi/2/68, H3N2)在BALB/c小鼠肺-肺模型上的适应过程。
2.制备银翘散水煎剂冻干样品并进行含量控制,为探讨银翘散抑制流感病毒机理提供物质基础。
3.考察银翘散样品体外抗甲型流感病毒H3N2的作用,比较细胞病变抑制法和空斑减少试验不同适用条件。
4.探讨银翘散样品体内抑制甲型流感病毒H3N2复制作用及途径。
方法：
1.以人类流感病毒株A/Aichi/2/68(H3N2)鼠肺-肺连续传代6次建立鼠肺适应株,比较每代适应株小鼠生存状态、肺指数、病毒滴度及血凝效价的改变,取第0、第6代鼠肺悬液进行NS1蛋白测序,找到野生株转变为适应株的突变氨基酸,探明突变发生过程中的关键事件。
2.采用高效液相色谱法分别测定银翘散中3味中药金银花、牛蒡子、甘草酸中绿原酸、牛蒡子苷、甘草酸含量,对自制银翘散水煎剂冻干样品进行质量控制。
3.细胞培养测定抗病毒效果。以细胞病变抑制法和空斑减少试验法,在不同试验策略(治疗、保护)下,评价银翘散体外抗流感病毒H3N2作用,比较2种方法不同适用条件。
4.H3N2鼠肺适应株滴鼻感染BALB/c小鼠,观察生存状态及检测肺指数；以苏木素-伊红染色(HE染色)法观察病理改变；透射电镜观察肺泡超微结构改变及病毒感染情况；将鼠肺悬液以空斑减少试验定量检测感染性病毒滴度,蛋白免疫印迹技术(western blot, WB)检测核蛋白(nucleoprotein, NP)表达。
结果：
1.第1代-第2代小鼠生存状态、鼠肺大体病变、肺指数、病毒滴度及血凝效价结果与正常对照组相比,差异无统计学意义(P>0.05)；第3代-第4代小鼠肺指数、病毒滴度及血凝效价逐渐升高；第5代、第6代小鼠出现耸毛,蜷缩,少食,少动,呼吸急促,进食、饮水量骤减,体重减轻等明显感染症状,鼠肺出现逐渐加重的水肿、淤血,呈肺肝样变,肺指数、病毒滴度、血凝效价结果与正常对照组比较,差异显著(P<0.01)；第6代鼠肺适应株NS1蛋白125位甘氨酸突变为天冬氨酸。
2.银翘散水煎剂冻干样品质控系统具有良好的稳定性和可重复性,受试样品中绿原酸、牛蒡子苷、甘草酸的含量符合现行药典标准。
3.体外抑制实验中,4～32mg/mL银翘散样品在治疗及保护模式下,均有较好的抑制病毒、提高细胞存活率的作用(P<0.01)；空斑减少试验结果显示4mg/mL银翘散样品两种模式SI分别为39.31及43.48,能有效抑制流感病毒,符合CPE的结果。
4.体内实验结果显示,银翘散大剂量(5g/kg)可以减轻全身症状,降低肺指数;改善鼠肺病变,范围<50%;减少肺泡腔渗出物、肺泡微细结构改变及病毒颗粒数量;降低鼠肺病毒滴度及鼠肺流感病毒核蛋白表达量,与模型对照组比较,差异具有统计学意义(P<0.05)。
结论：
1.该适应株模型提供了一个了解甲型流感病毒跨物种适应性的研究工具,不仅阐述了野生型流感病毒株在新宿主上产生适应性的过程,为探索适应过程中的病毒与宿主的分子变化打下基础,也为后续药理研究建立了平台,对于评价药物对H3N2流感病毒治疗效果及其作用机制具有重要意义。
2.银翘散冻干样品可以有效保护水煎液中有效成分,与传统剂型相比,易于标准定量,操控性强,适合进行药理及作用机制研究。
4.银翘散样品体外有抗甲型流感病毒H3N2的作用；MTT法适用于抗病毒药物初步筛选,而空斑减少试验适用于精确测定药物抗病毒活性。
5.银翘散样品体内有抑制甲1型流感病毒H3N2复制的作用,主要作用于病毒复制早期抑制NP蛋白合成过程中。
Objective:
1. Observe the adaptation process of Influenza A H3N2influenza virus (A/Aichi/2/68, H3N2) on BALB/c mouse lung model.
2. Establish a control method of Yinqiao powder freeze-dried sample, provide the material basis to explore the mechanism of inhibition of influenza virus by Yinqiao powder.
3. Inspect the antiviral effect of Yinqiao powder in vitro.
4. Explore the inhibition of viral replication by Yinqiao powder in vivo.
Methods:
1. The human influenza virus strains A/Aichi/2/68A (H3N2) as a research object, compared with survival status of mouse, pulmonary index, the virus titer and the hemagglutination titer of each generation, to find the changes of adaption strains between the wild strain and the mutation strain.
2. High performance liquid chromatography (HPLC) was used to determinate the quality of the honeysuckle, Arctium, glycyrrhizic acid.
3. Determined the antiviral effect by cell culture. Evaluated potency inhibition by the cytopathic effect (CPE) and the plaque reduction test method under different experimental strategies (treatment, protection)
4. We use BALB/c mice which were intranasal inoculated with H3N2strain of influenza A virus, to observe the living conditions, determinate lung index, to observed pathological changes by hematoxylin-eosin staining (HE staining), the alveolar ultrastructure changes by transmission electron microscopy; the mouse lung suspension were detected the quantity of infectious virus titer by reduced plaque test and the nucleoprotein (NP) expression by Western blot.
Results:
1. In the passage process of the mouse lung, the HA of human influenza virus H3N2changes to adapt to the new mouse host, with the125amino acid point of NS1protein mutations, the strain have more replication capacity, along with the viral titer increased, the mice began to appear towering hair, curled up, diet reduced, lack of exercise, shortness of breath, eating and drinking plummeted, weight loss and other symptoms of infection, mouse lungs emerge more and more severe edema, congestion and lung hepatization.
2. The quality control system of Yinqiao powder freeze-dried samples has good stability and repeatability, the chlorogenic acid, arctiin and licorice ammonium of this sample met the required of the national pharmacopoeia.
3. In vitro inhibition experiments, various concentrations of Yinqiao powder samples had better suppress the virus and cell survival effect (P<0.01) in the mode of treatment and protection; plaque reduction test results show that SI of two modes were39.31and43.48respectively, can effectively inhibit influenza virus, in line with the results of the CPE.
4. In vivo experimental results show that the Yinqiaosan sample can reduce the systemic symptoms, lung index, the scope of the rat lung lesions, alveolar space exudate, alveolar ultrastructure change and virus particle number; reduce mouse lung virus titers and mouse lung expression of nucleoprotein (nucleoprotein, NP).
Conclusion:
1. The adapted strains model provides an research tool to understanding the adaption of type A influenza virus cross-species, not only described the probably rocess of wild-type influenza virus strains in the new host adaptation, lay groundwork to explore the virus and its host the molecular changes in the process of adaptation, but also establish a platform for subsequent pharmacological studies, it has great significance for the evaluation antiviral effect and mechanism of drug treatment on H3N2influenza virus.
2. Yinqiao powder freeze-dried samples can effectively protect the active ingredient in the decoction, and compared to conventional formulations, get more easier standard quantitative, handling more suitable for the pharmacology and mechanism studies.
3. Yinqiao powder samples has anti-influenza A H3N2virus effect in vitro.
4. Yinqiao powder sample has inhibit replication of A type influenza virus H3N2in vivo, the major role is at the process of viral replication.
引文
[1]Hampson AW. Surveillance for pandemic influenza. J Infect Dis,1997,176:8-13.
[2]Cox NJ et al. Global epidemiology of influenza:past and present. Annu Rev Med,2000, 51:407-421.
[3]Tognotti E. Influenza pandemics:a historical retrospect. J Infect Dev Ctries,2009,3: 331-334.
[4]Glezen WP. Emerging infections:pandemic influenza. Epidemiol Rev,1996,18:64-76.
[5]盛丹,黎敬波,杨子峰,等.不同治法体内抗甲3(H_3N_2)亚型流感病毒作用的实验研究[J].河南中医,2007,27(2)：25-28.
[6]李兴旺.甲型H1N1流感-21世纪的第一次全球流感大流行[J].中华现代护理杂志,2009,15：1801-1803.
[7]王君,戴富强,刘敏,等.流行性感冒疫苗在小学生中临床效果及经济效益评估[J].流行病学杂志,2001,22：4771-4473.
[8]Anonymous. Invasion from the Steppes. Time,1978-2-20. http://www.time.com/time/ magazine/article/0,9171,948035,00.html
[9]郭元吉,程小雯.流行性感冒病毒及其实验技术[M].北京：中国三峡出版社,199787-88.
[10]陈彩粼译.2003-2004年全球流感疫情及2004-2005年流感疫苗组分建议[J].国外预防医学,2005,2(1)：封三.
[11]徐红.中国2002-2003年度流行性感冒监测分析[J].中华流行病学杂志,2003,24(11)：995-999.
[12]Ailonymous. Interactive health time line box 1977:Russianfluscare, CNN.
[13]潘曌曌.银翘散君臣药活性成分对IV增殖及IV肺炎小鼠细胞凋亡相关基因表达干预作用的研究.博士论文.辽宁中医药大学,2007.
[14]Stephen E L, Nancy J C, AlexanderK. Evolutionary analysis ofhumanH2N2 and earlyH3N2 influenza viruses:evidence for genetic divergence and multiple reassortment among H2N2 and/orH3N2 viruses [J]. Int Congr,2004,1263:184-190.
[15]CameronA S, RoderDM, EstermanA J, eta.l Mortality from influenza and allied infections in SouthAustralia during 1968-1981 [J]. Med J Aus,t 1985,142:14-17.
[16]Influenza in the world [J]. Wkly Epidemiol Rec,1969,44:12-27.
[17]Cockburn W C, Delon P J, FerreiraW. Origin and progress of the 1968-69 HongKong influenza epidemic [J]. Bull World Health Organ,1969,41:345-348.
[18]Lindstrom S E, CoxN J, KlimovA. Genetic analysis ofhumanH2N2 and earlyH3N2 influenza viruses,1957-1972:evidence for genetic divergence and multiple reassortment events [J]. Virology,2004,328:101-119.
[19]AirGM, ElsM C, Brown L E, eta.l Location of antigenic sites on the three-dimensional structure of the influenza N2 virus neuraminidase[J]. Virology,1985,145:237-248.
[20]Colman PM, Varghese JN, LaverW G. Structure of the catalytic and antigenic sites in influenza virus neuraminidase [J]. Nature,1983,303:41-44.
[21]Kilbourne E D. Perspectives on pandemics:a research agenda [J]. J InfectDis,1997, 176(Suppll):S29-31.
[22]MontoA S, KendalA P. Effectofneuraminidase antibody on Hong Kong influenza [J]. Lancet,1973,1:623-625.
[23]Longini IM Jr, Fine P E, Thacker S B. Predicting the global spread of new infectious agents[J]. Am Jepidemiol,1986,123:383-391.
[24]Stuart-Harris C. Epidemiology of influenza inman[J]. BrMed Bul,l 1979,35:3-8.
[25]Viboud C, GraisR F, LafontB A, et a.l. Multinational impactof the 1968HongKong pandemic:evidence for a smoldering pandemic [J]. J Infect Dis,2005,192:223-248.
[26]MillerD L, PereiraM S, ClarkeM. Epidemiology of theHongKong 68 variantof influenzaA2 in Britain [J]. BrMed J,1971,1:475-479.
[27]Stuart-HarrisCH. Pandemic influenza:an unresolved problem in prevention [J]. J InfectDis,1970,122:108-115.
[28]Noble G R. Epidemiological and clinical aspects of influenza. In basic and applied influenza research [M]. ed. AS Beare, Boca Raton, FL:CRC.1982:11-50.
[29]李龙芸,王孟昭.流感的流行特征[J].中国临床医学,2001,8：580.
[30]CecileV, RebeccaFG, BernardA P Lafon,t et a.l Multinational impactof the 1968 HongKong influenza pandemic:evidence for a smoldering pandemic [J]. J Infect Dis,2005, 192:233-248.
[31]Wile D C, Wilson I A, Skehel J J, et al. Structural identification of the antibody binding sites of Hong Kong influenza hemagglutinin and their involvement in antigenic variation. Nature,1981,289:373-378.
[32]Weis W, Brown J H, Cusack S, et all Structure of the influenza virus haemagglutinin complexed with its receptor, sialicacid. Nature,1998,333:426-431.
[33]Fitch W M, Bush R M, Bender C A, et al. Long term trends in the evolution of H (3) HA1 human influenza type A. Proc Natl Acad1 Sci USA,1997,94:7712-7718.
[34]Bush R M, Bender C A, Subbarao K, et al. Predicting the evolution of human influenza A. Science,1999,286:1921-1925.
[35]郭元吉,徐西雁,王敏,等.1979-1992年H3N2亚型流感病毒的血凝索J基因进化的研究[J].中华实验和临床病毒学杂志,1994,84：291-296.
[36]张烨,温乐英,李梓,等.2000-2002年我国流行的甲3(H3N2)亚型流感病毒抗原性及基因特性的研究[J].中华实验和临床病毒学杂志,2004,18(1)：16-19.
[37]张烨,李梓,郭俊峰,等.中国2000-2001年流行性感冒流行概论[J].中华流行病学杂志,2003,24(1)：4-6.
[38]王勇,陈淑霞,薛颖,等.中国历年H3N2亚型人流感病毒血凝素基因的序列测定及分析[J].病毒学报,2002,18(2)：118-125.
[39]董丽波,张烨,温乐英,等.1995-2005年中国H3N2亚型人流感病毒血凝素基因变异与流行相关性研究[J].病毒学报,2007,24(5)：339-344.
[40]Gupta V, Earl D J, Deem M W, et all Quantifying influenza vaccine efficacy and antigenic distance. Vaccine,2006,24 (18):3881-3888.
[41]Wolf Y I, Vibound C, Holmes E C, et al. Long interval of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus. Biology Direct,2006,1:34.
[42]黄文林主编.分子病毒学[M].北京：人民出版社,2002,8：285-286.
[43]Ilyinskii PO, Gabai VL, Sunyaev SR, et al. Toxicity of influenza A virus matrix protein 2 for mammalian cells is associated with its intrinsic proton-channeling activity. Cell Cycle,2007,6(16):2043-2047.
[44]De Clercq E. Antiviral agents active against influenza A viruses. Nat Rev Drug Discov, 2006,5(12):1015-1025.
[45]He G, Qiao J, Dong C, He C, et al. Amantadine-resistance among H5N1 avian influenza viruses isolated in Northern China Antiviral Res,2008,77(1):72-76.
[46]Hurt AC, Selleck P, Komadina N, et al. Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes. Antiviral Res, 2007; 73(3):228-231. Epub 2006 Nov 10.
[47]Nieholas KG, Aoki FY, Osterhaus ADME, et al. Efficacy and safety of Osttamivir in treatment of acute influenza. Lancet,2000,355(9218):1845-1851.
[48]陈忠斌,王升启.硫代反义寡核苷酸在细胞培养内抗甲型流感病毒活性[J].病毒学报,1998,14(3)：193-198.
[49]S Zhou, R Liu, BM Baroudy, et al. The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic rep licon RNA. Virology,2003,310 (2):333-337.
[50]李琦涵,姜莉.病毒感染的分子生物学[M].第一版.北京：化学工业出版社.2004：19-30.
[51]Suarez DL, et al. Comparisons of highly virulent H5N1 influenza A virus isolated from human sandchickens from Hong Kong. Virology,1998,72:6678-6688.
[52]Stamboulian D, Bonvehi PE. Influenza. Infect Dis Clin North Am,2000,14:141-149.
[53]中华人民共和国卫生部.中国流行性感冒疫苗预防接种指导意见[J].国际呼吸杂志,2006,26：3-7.
[54]Chen Z, Kadowaki S, Hagiwara Y, et al. Cross-protection against a lethal influenza virus infection by DNA vaccine. Vaccine,2001,18:3214-3221.
[55]张晏豪.银翘散加减治疗皮肤病的文献研究.硕士论文.北京中医药大学,2009.
[56]Hayden, F.G., Osterhaus, A.D., Treanor, J.J., Fleming, D.U., Aoki, F.Y., Nicholson, M.D., Bdinen, A.M., Hirst, H.M., Keene, O., Wightman, K.. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. New Engl. J. Med,1997,337,874-880.
[57]Buxton, R.C., Edwards, B., Juo, R.R., Voyta, J.C., Tisdale, M., Bethell, R.C.. Development of a sensitive chemiluminescent neuraminidase assay for the determination of influenza virus susceptibility to zanamivir. Anal. Biochem,2000,280,291-300.
[58]Appleyard, G, Maber, H.B.. Plaque formation by influenza viruses in the presence to trypsin. J. Gen. Virol,1974,25,351-357.
[59]Stuart-Harris, C.H., Schild, G.C.. The molecular virology and replication of influenza viruses. In:Influenza, The Viruses and the Disease. Publishing Science Group,1976, Littleton, pp,22-50.
[60]Sidwell, R.W., Huffman, J.H.. Use of disposable micro tissue culture plates for antiviral and interferon induction studies. Appl. Microbiol,1971,22,797-801.
[61]Henle, W. Multiplication of influenza virus in the ectodermal cells of the allantois of the chick embryo. Adv. Virus Res,1953,1,142-147.
[62]Rimmelzwaan, G.F., Baars, M., Claas, E.C., Osterhaus, A.D. Comparison of RNA hybridization, hemagglutination assay, titration of infectious virus and immunofluorescence as methods for monitoring influenza virus replication in vitro. J. Virol. Methods,1998,74, 57-66.
[63]Potter, C.W., Phair, J.P., Vodinelich, L., Fenton, R., Jennings, R. Antiviral, immunosuppressive, and antitumour effects of ribavirin. Nature,1976,259,496-497.
[64]Cochran, K.W., Maasab, H.F., Tsunoda, A., Berlin, B.S. Studies on the antiviral activity of amantadine ydrochloride. Ann. New York Acad. Sci.1965,130,432-439.
[65]Squires, S.L. The evaluation of compounds against influenza virus. Ann. New York Acad. Sci,1970,173,239-248.
[66]Hoffman, C.E. Amantadine HC1 and related compounds. In:Carter, W.A. (Ed.), Selective Inhibitors of Viral Functions. CRC Press, Boca Raton,1973, pp.199-212.
[67]Fenton, R.J., Morley, P.J., Owens, I.J., Gower, D., Parry, S., Crossman, L., Weng, T. Chemoprophylaxis of influenza A virus infections with single doses of zanamivir, demonstrates that zanamivir is cleared slowly from the respiratory tract. Antimicrob. Agents Chemother.1999,43,2642-2647.
[68]Blick, T.J., Sahasrabudhe, A., McDonald, M., Owens, I.J., Morley, P.J., Fenton, R.J., McKinn-Breshkin, J.L. The interaction of neuraminidase and hemagglutinin mutations in influenza virus in resistance to 4-guanidino-Neu4Ac2en. Virology,1998,246,95-103.
[69]Gubareva, L.V., Matrosovich, M.N., Brenner, M.K., Bethell, R.C., Webster, R.G. Evidence for zanamivir resistance in an immunocompromised child infccted with influenza B virus. J. Infect. Dis,1998,178,1257-1262.
170] Sugg, J.Y. An influenza virus pneumonia of mice that is not-transferable by serial passage. J. Bacteriol,1949,57,399-403.
[71]Ryan, D.M., Ticehurst, J., Dempsey, M.H., Penn, C.R. Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid) is consistent with extracellular activity of viral neuraminidase (sialidase). Antimicrob. Agents Chemother,1994,38,2270-2275.
[72]Sidwell, R.W., Huffman, J.H., Barnard, D.L., Bailey, K.W., Wong, M.H., Morrison, A., Syndergaard, T., Kim, C.U. Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor. Antiviral. Res,1998,37, 107-120.
[73]Sidwell, R., Huffman, J., Gilbert, J., Moscon, B., Pedersen, G., Burger, R., Warren, R. Utilization of pulse oximetry for the study of the inhibitory effects of antiviral agents on influenza virus in mice. Antimicrob. Agents Chemother,1992,36,473-476.
[74]McCauley, J.W., Pullen, L.A., Forsyth, M., Penn, C.R., Thomas, G.P. 4-guanidino-Neu5Ac2en fails to protect chickens from infection with highly pathogenic avian influenza virus. Antiviral Res,1995,27,179-186.
[75]Hayden, F.G., Belshe, R.B., Clover, R.D., Hay, A.J., Oakes, M.G., Soo, W. Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. New Engl. J. Med,1989,321,1696-1702.
[76]Englund, J.A., Champlin, R.E., Wyde, P.R., Kantarjian, H., Atmar, R.L., Tannand, J., Yousuf, H., Regnery, H., Klimov, A.I., Cox, N.J., Whimbey, E. Common emergence of amantadine-and rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults. Clin. Infect. Dis,1998,26,1418-1424.
[77]Mendel, D.B., Sidwell, R.W. Influenza virus resistance to neuraminidase inhibitors. Drug Resist,1998, Updates 1,184-189.
[78]Gubareva, L.V., Kaiser, L., Hayden, F.G. Influenza virus neuraminidase inhibitors. Lancet,2000,355,827-835.
[79]Gubareva, L.V., Robinson, M.J., Bethell, R.C., Webster, R.G. Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4guanidinoneu5Ac2en. J. Virol,1997,71,3385-3390.
[80]Tai, C.Y., Escarpe, P.A., Sidwell, R.W., Williams, M.A., Lew, W., Wu, H., Kim, C.U., Mendel, D.B. Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS4071. Antimicrob. Agents Chemother,1998,42, 3234-3241.
[81]Lightman, S., Cobbold, S., Waldmann, H., Askonas, B.A. Do L3T4- T cells act as effector cells in protection against influenza virus infection? Immunology,1987,62, 139-144.
[82]McKimm-Breschkin, J.L. Resistance of influenza viruses to neuraminidase inhibitors-a review. Antiviral Res,2000,47,1-17.
[83]Eichelberger, M., Allan, W., Zijlstra, M., Jaeniseh, R., Doherty, P.C. Clearance of influenze virus respiratory infection in mice lacking class I major histocompatibilily complex-restricted CD8+ T cells. J. Exp. Med,1991,174,875-880.
[84]Bender, B.S., Croghan, T., Zhang, L., Small, P.A., Jr. Transgenic mice lacking class Ⅰ major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J. Exp. Med,1992,175,1143-1145.
[85]Renegar, K.B., Small, P. A., Jr. Passive transfer of local immunity to influenza virus infection by IgA antibody. J. Immunol,1991,146,1972-1978.
[86]Mazanec, M.B., Kaetzel, C.S., Lamm, M.E., Fletcher, D., Nedrud, J.G. Intracellular neutralization of virus by immunoglobulin A antibodies. Proc. Natl. Acad. Sci. USA,1992, 89,6901-6905.
[87]Green, J.A., Charette, R.P., Yeh, T.-J., Smith, C.B. Presence of interferon in acute- and convalescent-phase sera of humans with influenza or an influenza-like illness of undetermined etiology. J. Infect. Dis,1982,145,837-842.
[88]Came, P.E., Lieberman, M, Pascale, A., Shimonaski, G. Antiviral activity of an interferon-inducing synthetic polymer. Proc. Soc. Exp. Biol. Med,1969,131,443-446.
[89]Gerone, P.J., Hill, D.A., Appell, L.H., Baron, S. Inhibition of respiratory virus infections of mice with aerosols of synthetic double-stranded ribonucleic acid. Infect. Immun,1971,3,323-327.
[90]Hill, D.A., Baron, S., Perkins, J.C., Worthington, M., Van Kirk, J.E., Mills, J., Kapikian, A.Z., Chanock, R.M. Evaluation of an interferon inducer in viral respiratory disease. J. Am. Med. Assoc,1972,219,1179-1184.
[91]Hennet, T., Ziltener, H.J., Frei, K., Peterhans, E. A kinetic study of immune mediators in the lungs of mice infected with influenza A virus. J. Immunol,1992,149,932-939.
[92]Rocha, E., Cox, N.J., Black, R.A., Harmon, M.W., Harrison, C.J., Kendal, A.P. Antigenic and genetic variation in influenza A (H1N1) virus isolates recovered from a persistently infected immunodeficient child. J. Virol,1991,65,2340-2350.
[93]Klimov, A.I., Rocha, E., Hayden, F.G., Shult, P.A., Roumillat, L.F., Cox, N.J. Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients:detection by polymerase chain reaction-restriction analysis. J. Infect. Dis,1995, 172,1352-1355.
[94]Sable, C.A., Hayden, F.G. Orthomyxoviral and paramyxoviral infection in transplant patients. Infect. Dis. Clin. North Am,1995,9,987-1003.
[95]Dong, L., Mori, I., Hossain, M.J., Kimura, Y. The senescene-accelerated mouse shows aging-related defects in cellular but not humoral immunity against influenza virus infection. J. Infect. Dis,2000,182,391-396.
[96]Sidwell, R., Smee, D.F., Morrey, J.D., Bailey, K.W., Bush, K. Effect of oral treatment with the neuraminidase inhibitor RWJ-270201 on influenza virus infections in immunosuppressed mice. Eleventh International Symposium on Infections in the Immunocompromised Host,2000,5:0-8.
|97] M.D. de Jong, C.P. Simmons, T.T. Thanh, V.M. I lien, G.J. Smith, T.N. Chau, D.M. Hoang, N.V. Chau, T.H. Khanh, V.C. Dong, P.T. Qui, B.V. Cam, Q. Hado, Y. Guan, J.S. Peiris, N.T. Chinh, T.T. Hien, J. Farrar, Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat. Med,2006,12:1203-1207.
[98]T.M. Tumpey, T.R. Maines, N. Van Hoeven, L. Glaser, A. Solorzano, C. Pappas, N.J. Cox, D.E. Swayne, P. Palese, J.M. Katz, A. Garcia- Sastre, A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science,2007,315: 655-659.
[99]S.K. Lai, V.T.K. Chow, Avian influenza H5N1 virus:an emerging global pandemic, in: S.K. Lai (Ed.), Emerging Viral Diseases of Southeast Asia, Karger, Basel.2007, pp.59-77.
[100]V.T. Chow, P.A. Tambyah, K.T. Goh, To kill a mocking bird flu? Ann. Acad. Med. 2008,37:451-453.
[101]R.G. Webster, K.F. Shortridge, Y. Kawaoka, Influenza:interspecies transmission and emergence of new pandemics, FEMS Immunol. Med. Microbiol.1997,18:275-279.
[102]J.C. de Jong, E.C. Claas, A.D. Osterhaus, R.G. Webster, W.L. Lim, A pandemic warning? Nature.1997,389:554-560.
[103]J.K. Taubenberger, D.M. Morens,1918 influenza:the mother of all pandemics. Emerg. Infect. Dis.2006,12:15-22.
[104]De Jong J C, Rimmelzwaan G F, Fouchier R A, Osterhaus A D. Influenza virus:a master of metamorphosis. J Infect.2000,40:218-228.
[105]Horimoto T, Kawaoka Y. Influenza:lessons from past pandemics, warnings from current incidents. Nat Rev Microbiol.2005,3:591-600.
[106]E.D. Kilbourne, In pursuit of influenza:Fort Monmouth to Valhalla (and back). Bioessays.1997, (19):641-650.
[107]A.C. Ward, Virulence of influenza A virus for mouse lung. Virus Genes.1997, (14):187-194.
[108]X. Lu, T.M. Tumpey, T. Morken, S.R. Zaki, N.J. Cox, J.M. Katz. A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. J. Virol.1999, (73):5903-5911.
[109]G.F. Rimmelzwaan, D. van Riel, M. Baars, T.M. Bestebroer, G. van Amerongen, R.A. Fouchier, A.D. Osterhaus, T. Kuiken. Influenza Avirus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am. J.Pathol.2006, (168):176-183.
[110]E.G. Brown. Increased virulence of a mouse-adapted variant of influenza A/FM/1/47 virus is controlled by mutations in genome segments 4,5,7, and 8. J. Virol.1990, (64): 4523-4533.
[111]E.G. Brown, H. Liu, L.C. Kit, S. Baird, M. Nesrallah. Pattern of mutation in the genome of influenza Avirus on adaptation to increased virulence in the mouse lung: identification of functional themes. Proc. Natl. Acad. Sci. U.S.A.2001, (98):6883-6888.
[112]C.A. Smeenk, E.G. Brown. The influenza virus variant A/FM/1/47-MA possesses single amino acid replacements in the hemagglutinin, controlling virulence, and in the matrix protein, controlling virulence as well as growth. J. Virol.1994, (68):530-534.
[113]T. Ito, Y. Suzuki, L. Mitnaul, A. Vines, H. Kida, Y. Kawaoka. Receptor specificity of influenza A viruses correlates with the agglutination of erythrocytes from different animal species. Virology.1997, (227):493-499.
[114]A. Ibricevic, A. Pekosz, M.J. Walter, C. Newby, J.T. Battaile, E.G. Brown, M.J. Holtzman, S.L. Brody. Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cells. J. Virol.2006, (80):7469-7480.
[115]J. Meisner, K.J. Szretter, K.C. Bradley, W.A. Langley, Z.N. Li, B.J. Lee, S. Thoennes, J. Martin, J.J. Skehel, R.J. Russell, J.M. Katz, D.A. Steinhauer. Infectivity studies of influenza virus hemagglutinin receptor binding site mutants in mice. J. Virol.2008, (82): 5079-5083.
[116]孙惠惠.H1N1小鼠模型的建立及板蓝根颗粒对H1N1模型小鼠的作用的研究.硕士论文.北京协和医学院,2010.
[117]E.G. Brown. Increased virulence of a mouse-adapted variant of influenza A/FM/1/47 virus is controlled by mutations in genome segments 4,5,7, and 8. J. Virol 1990, (64): 4523-4533.
[118]Y. Furuta, K. Takahashi, Y. Fukuda,et al. In vitro and in vivo activities of anti-influenza virus compound T-705.Antimicrob. agents chemother.2002, (46):977-981.
[119]Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg,1938, (27):493-497.
[120]Suzuki, Y. Sialobiology of Influenza:Molecular Mechanism of Host Range Variation of Influenza Viruses. Biological and Pharmaceutical Bulletin,2005,28,399-408.
[121]Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, Klimov A. Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology,2006,344(2), 432-438.
[122]Krug RM, Yuan W, Noah DL, et al. Intracellular warfare between human influenza viruses and human cells:the roles of the viral NS1 protein. Virology.2003,309(2):181-189.
[123]Enami M, Enami K. Characterization of influenza virus NS1 protein by using a novel helper-virus-free reverse genetic system. J Hrol,2000,74(12):5556-5561.
[124]Chien C, Tejem R, Huang Y, et al. A novel RNA-binding motif in influenza A virus non-structural protein. Nat Strttct Biol,1997,4 (11):891-895.
[125]Liu J, Lynch, PA, Chien C, et al. Crystal structure of the unique multifunctional RNA binding domain of the influenza virus NS1 protein. Nat Strttct BIO,1997,4(11):896-899.
[126]Idoia B, Tomas A, Juan O, et al. PABPI and eIF4GI associate with influenza virus NSI protein in viral mRN A translation initiation complexes. Journal of General Virology, 2003,84(12):3263-3274.
[127]Falc6n AM, MaTi6n RM, ZOrcher TZ, et al. Defective RNA replication and late gene expression in temperature-sensitive Influenza viruses expressing deleted forms of the NS1 protein. Virol,2004,78(8):3880-3888.
[128]Bomholdt ZA, Prazad BV. X-ray structure of influenza virus NS1 effactor domain. Nat Stn Mol BIof,2006,13(6):559-560.
[129]Obenauer JC, Denson J, Perdeep K. Large-Scale sequence analysis of avian influenza isolates. Science,2006,311(5767):1576-1580.
[130]张丹桂,李卫中,王革非,等.A型流感病毒NS1蛋白羧基端PL结构域影响NS1在细胞核内的定位[J].生物化学与生物物理进展,2010,37(9)：975-982.
[131]Falc6n A, Fortes P, MaTi6n RM, et al. Interaction of influenza virus NSI protein and the human homologue of Staufen in vivo and in vitro. Nucleic Acids Res,1999,7(11):2241-2247.
[132]Thomas A, Susana de la Luna, Isabel N, et al. Eukaryotic translation initiation factor 4GI is a cellular target for NS 1 protein, a translational activator of influenza virus. Molecular and Cellular Biology,2000,20(17):6259-6268.
[133]Wolf T, O'Neil R E, Palese P. Interaction cloning of NS1-I, a human protein that binds to the nonstructural NS1 proteins of influenza A and B viruses. J Virol,1996,70(8): 5363-5372.
[134]张玲,尚立霞,单卫华,等.金银花提取工艺研究[J].中药新药与临床药理,2003,14(1)：59-61.
[135]丁利君,吴振辉,蔡创海,等.金银花中黄酮类物质最佳提取工艺的研究[J].食品科学,2002,23(2)：62-65.
[136]胡克杰,孙考祥,王璐,等.绿原酸体外抗病毒作用研究[J].哈尔滨医科大学学报,2001,35(6)：430-432.
[137]王发国,叶华谷,马其侠,等.金银花及其药理作用[J].生物学通报,2004,39(5)：17-18.
[138]M. Nose, et al. Structural transformation of lignan compounds in rat gastrointestinal tract [J]. Planta Med.1992,58(6):520-523.
[139]Yao X J, Mark A, et al. Mechanism of inhibition of HIV-1 infection in vitro by purified extract of prunella vulgaris[J]. Virology.1992,187:56-58.
[140]高洋,等.牛蒡苷元体外抗流感病毒活性[J].中草药.2002,33(8)：724-726.
[141]高阳,董雪,康廷国,等.牛蒡子苷元体外抗流感病毒活性[J].中草药,2002,33(8)：724-726.
[142]杨子峰,刘妮,黄碧松,等.牛蒡苷元体内抗甲I型流感病毒作用的研究[J].中草药,2005,28(11)：1012-1014.
[143]Hisami W, Chikako M, Masahiko M, et al. Therapeutic effects of glycyrrhizin in mice infected with LP-BM5 murineretro virus and mechanisms involved in the prevention of disease progression[J]. Biotherapy,1996,9(4):209-220.
[144]Shigeyoshi H, Toshiro M, Eiji H, et al. Biochemical characterization of recombinant HIV-1 reverse transcriptase (rRT) as a glycyrrhizin- binding protein and t he CK-Ⅱ mediated stimulation of rRT activity potently inhibited by glycyrrhetinic acid derivative[J]. Biol Pharm Bull,1998,21(12):1282-1285.
[145]Sasaki H, Takei M, Kobayashi M, et al. Effect o f glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV-sero positive patients[J]. Pathobiology,2002-2003,70(4):229-236.
[146]陈宇萍,刘新记,刘克锋,等.复方甘草酸苷注射液治疗传染性非典型肺炎的临床观察[J].中国药房,2004,15(5)：294-295.
[147]Hoever G, Baltina L, Michaelis M, et al. Antiviral Activity of glycyrrhizin acid derivatives against SARS-corona virus [J]. J Med Chem,2005,48(4):1256-1259.
[148]Wu C Y, King K Y, Kuo C J, et al. Stable benzotriazole esters as mechanism-based inactivato rs of the severe acute respiratory syndrome 3CL protease [J]. Chemistry & Biology,2006,13(3):261-268.
[149]Matsuo K, Takenaka K, Shimomur a H, et al. Lamivudine and g lycyrrhizin for treatment of chemotherapy-induced hepatitis B virus (HBV) hepatitis in a chronic HBV carrier with non-Hodgkin lymphoma [J]. Leuk Lymphoma,2001,41 (1-2):191-195.
[150]张压西.复方甘草酸苷治疗慢性乙型肝炎的临床疗效及抗病毒作用观察[J].传染病信息,2005,18(2)：89-90.
[151]何卫东,徐秉坤.复方甘草酸苷注射液治疗带状疱疹疗效观察[J].中国药房,2004,15(11)：688-690.
[152]Arjun R, Mabalirajan U, Moumita D, et al. Glycyrrhizin alleviates experimental allergic asthma in mice [J]. International Immunopharmacology,2006,6:1468-1477.
[153]王秀琴,李洪源,刘鑫妍.甘草抗病毒有效部位(GD4)体外抑制呼吸道合胞病毒性作用的研究[J].中药材,2006,29(7)：692-694.
[154]刘舒,韩静,工绿娅.黄酮、异黄酮药物抑制肿瘤细胞增殖作用的最近进展[J].中国药学杂志,2004,39(1)：41-43.
[155]Clercq E D. Potential antivirals and antiviral strategies against SARS corona virus infections [J]. Expert Rev Anti Infect Ther,2006,4(2):291-302.
[156]Pompei R, Pag hi L, Ing ianni A, et al. Glycyrrhizic acid inhibits influenza virus growth in embryonated eggs[J]. Microbiologica,1983,6(3):247-250.
[157]Utsunomiya T, Kobay ashi M, Pollard R B, et al. Glycyrrhizin, an active component of licorice roots, r educes morbidity and mortability of mice infected wit h lethal dose of influenza v irus [J]. Antimicrob Agents Chemo ther,1997,41 (3):551.
[158]刘汉清,刘嘉.中药冻干制剂相关技术应用研究概药[C].中华中医药学会第九届制剂学术研讨会论文汇编.长春.中国.2008.
[159]de Clercq E. Antiviral drugs in current clinical use[J]. Journal of Clinical Virology, 2004,30(2):115.
[160]Ilyushina N A, Elena A, Govorkova, et al. Detection of amantadine-resistant variants among avian influenza viruses isolated in North America and Asia[J]. Virology,2005, 341(1):102.
[161]龚震宇,杨小平.2009年甲型流感(H1N1)大流行病毒对达菲的耐药情况[J].疾病监测,2009,24(12)：983.
[162]Chen J X, Xue H J, Ye W C, et al. Activity of Andrographolide and Its Derivatives against Influenza Virus in Vivo and in Vitro[J]. Biol Pharm Bull,2009,32(8):1385.
[163]Ehrhardt,C,Hrincius,ERIKorte,V. CYSTUS052, exerts anti influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance. Antiviral Research.2007,76(1):38.
[164]Reed LJ, Muench H. A simple method of estimating fifty percent endpoints[J]. Am J Hyg,1938,27:493.
[165]R. Ian Freshney. Animal Cell Culture, a Practical approach[M]. Oxford University Press,1992.361
[166]Knox YM, Suzutani T, Yosida I, et al. Anti-influenza virus activity of crude extract of Ribes nigrum L[J].Phytother Res.2003; 17(2):120.
[167]Y Furuta, K Takahashi, Y Fukuda, et al. In vitro and in vivo activities of anti-influenza virus compound T-705[J].Antimicrob Agents Chemother.2002; 46 (4):977.
[168]刘崇海,皮光环,王莉佳,等.噻唑蓝(MTT)法空斑形成实验在病毒检测中的应用[J].川北医学院学报,2010,25(6)：509-512.
[169]徐淑云,卞如濂,陈修.药理实验方法学[M].3版.北京：人民卫生出版社,2001.226-234,1720-1740.9(专著)
[170]Szapiel SV, Elson NA, Fulmer TD, et al. Bleomycin2induced in2 terstitial pulmonary disease in the Nude, Athymic mouse [J]. Am Rev Respir Dis,1979, 120:8932899.
[171]Y. Furuta, K. Takahashi, Y. Fukuda,et al.In vitro and in vivo activities of anti-influenza virus compound T-705.Antimicrob [J]. agents chemother.2002; 46 (4): 977-81.
[172]Reed LJ, Muench H. A simple method of estimating fifty percent endpoints [J]. Am J Hyg,1938,27(3):493-497.
[173]罗凤岩,王淑梅.银翘散临床应用概述[JJ.现代中西医结合杂志,2009,18(30)：3781-3783.
[174]白刚.中药方剂研究与应用大全[M].北京：中国科学技术出版社,1995：972.
[175]何建萍.银翘散的临床药理[J].中]国实用医药,2009,4(23)：149-150.
[176]刘亚娴,霍炳杰,张莉,刘羽,李晶.银翘散在不同煎煮时间下对免疫抑制小鼠的免疫调节作用[J].中医杂志,2008,49(12)：1112-1115.
[2]Cox NJ et al. Global epidemiology of influenza:past and present. Annu Rev Med,2000, 51:407-421.
[3]Tognotti E. Influenza pandemics:a historical retrospect. J Infect Dev Ctries,2009,3: 331-334.
[4]Glezen WP. Emerging infections:pandemic influenza. Epidemiol Rev,1996,18:64-76.
[5]盛丹,黎敬波,杨子峰,等.不同治法体内抗甲3(H_3N_2)亚型流感病毒作用的实验研究[J].河南中医,2007,27(2)：25-28.
[6]李兴旺.甲型H1N1流感-21世纪的第一次全球流感大流行[J].中华现代护理杂志,2009,15：1801-1803.
[7]王君,戴富强,刘敏,等.流行性感冒疫苗在小学生中临床效果及经济效益评估[J].流行病学杂志,2001,22：4771-4473.
[8]Anonymous. Invasion from the Steppes. Time,1978-2-20. http://www.time.com/time/ magazine/article/0,9171,948035,00.html
[9]郭元吉,程小雯.流行性感冒病毒及其实验技术[M].北京：中国三峡出版社,199787-88.
[10]陈彩粼译.2003-2004年全球流感疫情及2004-2005年流感疫苗组分建议[J].国外预防医学,2005,2(1)：封三.
[11]徐红.中国2002-2003年度流行性感冒监测分析[J].中华流行病学杂志,2003,24(11)：995-999.
[12]Ailonymous. Interactive health time line box 1977:Russianfluscare, CNN.
[13]潘曌曌.银翘散君臣药活性成分对IV增殖及IV肺炎小鼠细胞凋亡相关基因表达干预作用的研究.博士论文.辽宁中医药大学,2007.
[14]Stephen E L, Nancy J C, AlexanderK. Evolutionary analysis ofhumanH2N2 and earlyH3N2 influenza viruses:evidence for genetic divergence and multiple reassortment among H2N2 and/orH3N2 viruses [J]. Int Congr,2004,1263:184-190.
[15]CameronA S, RoderDM, EstermanA J, eta.l Mortality from influenza and allied infections in SouthAustralia during 1968-1981 [J]. Med J Aus,t 1985,142:14-17.
[16]Influenza in the world [J]. Wkly Epidemiol Rec,1969,44:12-27.
[17]Cockburn W C, Delon P J, FerreiraW. Origin and progress of the 1968-69 HongKong influenza epidemic [J]. Bull World Health Organ,1969,41:345-348.
[18]Lindstrom S E, CoxN J, KlimovA. Genetic analysis ofhumanH2N2 and earlyH3N2 influenza viruses,1957-1972:evidence for genetic divergence and multiple reassortment events [J]. Virology,2004,328:101-119.
[19]AirGM, ElsM C, Brown L E, eta.l Location of antigenic sites on the three-dimensional structure of the influenza N2 virus neuraminidase[J]. Virology,1985,145:237-248.
[20]Colman PM, Varghese JN, LaverW G. Structure of the catalytic and antigenic sites in influenza virus neuraminidase [J]. Nature,1983,303:41-44.
[21]Kilbourne E D. Perspectives on pandemics:a research agenda [J]. J InfectDis,1997, 176(Suppll):S29-31.
[22]MontoA S, KendalA P. Effectofneuraminidase antibody on Hong Kong influenza [J]. Lancet,1973,1:623-625.
[23]Longini IM Jr, Fine P E, Thacker S B. Predicting the global spread of new infectious agents[J]. Am Jepidemiol,1986,123:383-391.
[24]Stuart-Harris C. Epidemiology of influenza inman[J]. BrMed Bul,l 1979,35:3-8.
[25]Viboud C, GraisR F, LafontB A, et a.l. Multinational impactof the 1968HongKong pandemic:evidence for a smoldering pandemic [J]. J Infect Dis,2005,192:223-248.
[26]MillerD L, PereiraM S, ClarkeM. Epidemiology of theHongKong 68 variantof influenzaA2 in Britain [J]. BrMed J,1971,1:475-479.
[27]Stuart-HarrisCH. Pandemic influenza:an unresolved problem in prevention [J]. J InfectDis,1970,122:108-115.
[28]Noble G R. Epidemiological and clinical aspects of influenza. In basic and applied influenza research [M]. ed. AS Beare, Boca Raton, FL:CRC.1982:11-50.
[29]李龙芸,王孟昭.流感的流行特征[J].中国临床医学,2001,8：580.
[30]CecileV, RebeccaFG, BernardA P Lafon,t et a.l Multinational impactof the 1968 HongKong influenza pandemic:evidence for a smoldering pandemic [J]. J Infect Dis,2005, 192:233-248.
[31]Wile D C, Wilson I A, Skehel J J, et al. Structural identification of the antibody binding sites of Hong Kong influenza hemagglutinin and their involvement in antigenic variation. Nature,1981,289:373-378.
[32]Weis W, Brown J H, Cusack S, et all Structure of the influenza virus haemagglutinin complexed with its receptor, sialicacid. Nature,1998,333:426-431.
[33]Fitch W M, Bush R M, Bender C A, et al. Long term trends in the evolution of H (3) HA1 human influenza type A. Proc Natl Acad1 Sci USA,1997,94:7712-7718.
[34]Bush R M, Bender C A, Subbarao K, et al. Predicting the evolution of human influenza A. Science,1999,286:1921-1925.
[35]郭元吉,徐西雁,王敏,等.1979-1992年H3N2亚型流感病毒的血凝索J基因进化的研究[J].中华实验和临床病毒学杂志,1994,84：291-296.
[36]张烨,温乐英,李梓,等.2000-2002年我国流行的甲3(H3N2)亚型流感病毒抗原性及基因特性的研究[J].中华实验和临床病毒学杂志,2004,18(1)：16-19.
[37]张烨,李梓,郭俊峰,等.中国2000-2001年流行性感冒流行概论[J].中华流行病学杂志,2003,24(1)：4-6.
[38]王勇,陈淑霞,薛颖,等.中国历年H3N2亚型人流感病毒血凝素基因的序列测定及分析[J].病毒学报,2002,18(2)：118-125.
[39]董丽波,张烨,温乐英,等.1995-2005年中国H3N2亚型人流感病毒血凝素基因变异与流行相关性研究[J].病毒学报,2007,24(5)：339-344.
[40]Gupta V, Earl D J, Deem M W, et all Quantifying influenza vaccine efficacy and antigenic distance. Vaccine,2006,24 (18):3881-3888.
[41]Wolf Y I, Vibound C, Holmes E C, et al. Long interval of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus. Biology Direct,2006,1:34.
[42]黄文林主编.分子病毒学[M].北京：人民出版社,2002,8：285-286.
[43]Ilyinskii PO, Gabai VL, Sunyaev SR, et al. Toxicity of influenza A virus matrix protein 2 for mammalian cells is associated with its intrinsic proton-channeling activity. Cell Cycle,2007,6(16):2043-2047.
[44]De Clercq E. Antiviral agents active against influenza A viruses. Nat Rev Drug Discov, 2006,5(12):1015-1025.
[45]He G, Qiao J, Dong C, He C, et al. Amantadine-resistance among H5N1 avian influenza viruses isolated in Northern China Antiviral Res,2008,77(1):72-76.
[46]Hurt AC, Selleck P, Komadina N, et al. Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes. Antiviral Res, 2007; 73(3):228-231. Epub 2006 Nov 10.
[47]Nieholas KG, Aoki FY, Osterhaus ADME, et al. Efficacy and safety of Osttamivir in treatment of acute influenza. Lancet,2000,355(9218):1845-1851.
[48]陈忠斌,王升启.硫代反义寡核苷酸在细胞培养内抗甲型流感病毒活性[J].病毒学报,1998,14(3)：193-198.
[49]S Zhou, R Liu, BM Baroudy, et al. The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic rep licon RNA. Virology,2003,310 (2):333-337.
[50]李琦涵,姜莉.病毒感染的分子生物学[M].第一版.北京：化学工业出版社.2004：19-30.
[51]Suarez DL, et al. Comparisons of highly virulent H5N1 influenza A virus isolated from human sandchickens from Hong Kong. Virology,1998,72:6678-6688.
[52]Stamboulian D, Bonvehi PE. Influenza. Infect Dis Clin North Am,2000,14:141-149.
[53]中华人民共和国卫生部.中国流行性感冒疫苗预防接种指导意见[J].国际呼吸杂志,2006,26：3-7.
[54]Chen Z, Kadowaki S, Hagiwara Y, et al. Cross-protection against a lethal influenza virus infection by DNA vaccine. Vaccine,2001,18:3214-3221.
[55]张晏豪.银翘散加减治疗皮肤病的文献研究.硕士论文.北京中医药大学,2009.
[56]Hayden, F.G., Osterhaus, A.D., Treanor, J.J., Fleming, D.U., Aoki, F.Y., Nicholson, M.D., Bdinen, A.M., Hirst, H.M., Keene, O., Wightman, K.. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. New Engl. J. Med,1997,337,874-880.
[57]Buxton, R.C., Edwards, B., Juo, R.R., Voyta, J.C., Tisdale, M., Bethell, R.C.. Development of a sensitive chemiluminescent neuraminidase assay for the determination of influenza virus susceptibility to zanamivir. Anal. Biochem,2000,280,291-300.
[58]Appleyard, G, Maber, H.B.. Plaque formation by influenza viruses in the presence to trypsin. J. Gen. Virol,1974,25,351-357.
[59]Stuart-Harris, C.H., Schild, G.C.. The molecular virology and replication of influenza viruses. In:Influenza, The Viruses and the Disease. Publishing Science Group,1976, Littleton, pp,22-50.
[60]Sidwell, R.W., Huffman, J.H.. Use of disposable micro tissue culture plates for antiviral and interferon induction studies. Appl. Microbiol,1971,22,797-801.
[61]Henle, W. Multiplication of influenza virus in the ectodermal cells of the allantois of the chick embryo. Adv. Virus Res,1953,1,142-147.
[62]Rimmelzwaan, G.F., Baars, M., Claas, E.C., Osterhaus, A.D. Comparison of RNA hybridization, hemagglutination assay, titration of infectious virus and immunofluorescence as methods for monitoring influenza virus replication in vitro. J. Virol. Methods,1998,74, 57-66.
[63]Potter, C.W., Phair, J.P., Vodinelich, L., Fenton, R., Jennings, R. Antiviral, immunosuppressive, and antitumour effects of ribavirin. Nature,1976,259,496-497.
[64]Cochran, K.W., Maasab, H.F., Tsunoda, A., Berlin, B.S. Studies on the antiviral activity of amantadine ydrochloride. Ann. New York Acad. Sci.1965,130,432-439.
[65]Squires, S.L. The evaluation of compounds against influenza virus. Ann. New York Acad. Sci,1970,173,239-248.
[66]Hoffman, C.E. Amantadine HC1 and related compounds. In:Carter, W.A. (Ed.), Selective Inhibitors of Viral Functions. CRC Press, Boca Raton,1973, pp.199-212.
[67]Fenton, R.J., Morley, P.J., Owens, I.J., Gower, D., Parry, S., Crossman, L., Weng, T. Chemoprophylaxis of influenza A virus infections with single doses of zanamivir, demonstrates that zanamivir is cleared slowly from the respiratory tract. Antimicrob. Agents Chemother.1999,43,2642-2647.
[68]Blick, T.J., Sahasrabudhe, A., McDonald, M., Owens, I.J., Morley, P.J., Fenton, R.J., McKinn-Breshkin, J.L. The interaction of neuraminidase and hemagglutinin mutations in influenza virus in resistance to 4-guanidino-Neu4Ac2en. Virology,1998,246,95-103.
[69]Gubareva, L.V., Matrosovich, M.N., Brenner, M.K., Bethell, R.C., Webster, R.G. Evidence for zanamivir resistance in an immunocompromised child infccted with influenza B virus. J. Infect. Dis,1998,178,1257-1262.
170] Sugg, J.Y. An influenza virus pneumonia of mice that is not-transferable by serial passage. J. Bacteriol,1949,57,399-403.
[71]Ryan, D.M., Ticehurst, J., Dempsey, M.H., Penn, C.R. Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid) is consistent with extracellular activity of viral neuraminidase (sialidase). Antimicrob. Agents Chemother,1994,38,2270-2275.
[72]Sidwell, R.W., Huffman, J.H., Barnard, D.L., Bailey, K.W., Wong, M.H., Morrison, A., Syndergaard, T., Kim, C.U. Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor. Antiviral. Res,1998,37, 107-120.
[73]Sidwell, R., Huffman, J., Gilbert, J., Moscon, B., Pedersen, G., Burger, R., Warren, R. Utilization of pulse oximetry for the study of the inhibitory effects of antiviral agents on influenza virus in mice. Antimicrob. Agents Chemother,1992,36,473-476.
[74]McCauley, J.W., Pullen, L.A., Forsyth, M., Penn, C.R., Thomas, G.P. 4-guanidino-Neu5Ac2en fails to protect chickens from infection with highly pathogenic avian influenza virus. Antiviral Res,1995,27,179-186.
[75]Hayden, F.G., Belshe, R.B., Clover, R.D., Hay, A.J., Oakes, M.G., Soo, W. Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. New Engl. J. Med,1989,321,1696-1702.
[76]Englund, J.A., Champlin, R.E., Wyde, P.R., Kantarjian, H., Atmar, R.L., Tannand, J., Yousuf, H., Regnery, H., Klimov, A.I., Cox, N.J., Whimbey, E. Common emergence of amantadine-and rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults. Clin. Infect. Dis,1998,26,1418-1424.
[77]Mendel, D.B., Sidwell, R.W. Influenza virus resistance to neuraminidase inhibitors. Drug Resist,1998, Updates 1,184-189.
[78]Gubareva, L.V., Kaiser, L., Hayden, F.G. Influenza virus neuraminidase inhibitors. Lancet,2000,355,827-835.
[79]Gubareva, L.V., Robinson, M.J., Bethell, R.C., Webster, R.G. Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4guanidinoneu5Ac2en. J. Virol,1997,71,3385-3390.
[80]Tai, C.Y., Escarpe, P.A., Sidwell, R.W., Williams, M.A., Lew, W., Wu, H., Kim, C.U., Mendel, D.B. Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS4071. Antimicrob. Agents Chemother,1998,42, 3234-3241.
[81]Lightman, S., Cobbold, S., Waldmann, H., Askonas, B.A. Do L3T4- T cells act as effector cells in protection against influenza virus infection? Immunology,1987,62, 139-144.
[82]McKimm-Breschkin, J.L. Resistance of influenza viruses to neuraminidase inhibitors-a review. Antiviral Res,2000,47,1-17.
[83]Eichelberger, M., Allan, W., Zijlstra, M., Jaeniseh, R., Doherty, P.C. Clearance of influenze virus respiratory infection in mice lacking class I major histocompatibilily complex-restricted CD8+ T cells. J. Exp. Med,1991,174,875-880.
[84]Bender, B.S., Croghan, T., Zhang, L., Small, P.A., Jr. Transgenic mice lacking class Ⅰ major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J. Exp. Med,1992,175,1143-1145.
[85]Renegar, K.B., Small, P. A., Jr. Passive transfer of local immunity to influenza virus infection by IgA antibody. J. Immunol,1991,146,1972-1978.
[86]Mazanec, M.B., Kaetzel, C.S., Lamm, M.E., Fletcher, D., Nedrud, J.G. Intracellular neutralization of virus by immunoglobulin A antibodies. Proc. Natl. Acad. Sci. USA,1992, 89,6901-6905.
[87]Green, J.A., Charette, R.P., Yeh, T.-J., Smith, C.B. Presence of interferon in acute- and convalescent-phase sera of humans with influenza or an influenza-like illness of undetermined etiology. J. Infect. Dis,1982,145,837-842.
[88]Came, P.E., Lieberman, M, Pascale, A., Shimonaski, G. Antiviral activity of an interferon-inducing synthetic polymer. Proc. Soc. Exp. Biol. Med,1969,131,443-446.
[89]Gerone, P.J., Hill, D.A., Appell, L.H., Baron, S. Inhibition of respiratory virus infections of mice with aerosols of synthetic double-stranded ribonucleic acid. Infect. Immun,1971,3,323-327.
[90]Hill, D.A., Baron, S., Perkins, J.C., Worthington, M., Van Kirk, J.E., Mills, J., Kapikian, A.Z., Chanock, R.M. Evaluation of an interferon inducer in viral respiratory disease. J. Am. Med. Assoc,1972,219,1179-1184.
[91]Hennet, T., Ziltener, H.J., Frei, K., Peterhans, E. A kinetic study of immune mediators in the lungs of mice infected with influenza A virus. J. Immunol,1992,149,932-939.
[92]Rocha, E., Cox, N.J., Black, R.A., Harmon, M.W., Harrison, C.J., Kendal, A.P. Antigenic and genetic variation in influenza A (H1N1) virus isolates recovered from a persistently infected immunodeficient child. J. Virol,1991,65,2340-2350.
[93]Klimov, A.I., Rocha, E., Hayden, F.G., Shult, P.A., Roumillat, L.F., Cox, N.J. Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients:detection by polymerase chain reaction-restriction analysis. J. Infect. Dis,1995, 172,1352-1355.
[94]Sable, C.A., Hayden, F.G. Orthomyxoviral and paramyxoviral infection in transplant patients. Infect. Dis. Clin. North Am,1995,9,987-1003.
[95]Dong, L., Mori, I., Hossain, M.J., Kimura, Y. The senescene-accelerated mouse shows aging-related defects in cellular but not humoral immunity against influenza virus infection. J. Infect. Dis,2000,182,391-396.
[96]Sidwell, R., Smee, D.F., Morrey, J.D., Bailey, K.W., Bush, K. Effect of oral treatment with the neuraminidase inhibitor RWJ-270201 on influenza virus infections in immunosuppressed mice. Eleventh International Symposium on Infections in the Immunocompromised Host,2000,5:0-8.
|97] M.D. de Jong, C.P. Simmons, T.T. Thanh, V.M. I lien, G.J. Smith, T.N. Chau, D.M. Hoang, N.V. Chau, T.H. Khanh, V.C. Dong, P.T. Qui, B.V. Cam, Q. Hado, Y. Guan, J.S. Peiris, N.T. Chinh, T.T. Hien, J. Farrar, Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat. Med,2006,12:1203-1207.
[98]T.M. Tumpey, T.R. Maines, N. Van Hoeven, L. Glaser, A. Solorzano, C. Pappas, N.J. Cox, D.E. Swayne, P. Palese, J.M. Katz, A. Garcia- Sastre, A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science,2007,315: 655-659.
[99]S.K. Lai, V.T.K. Chow, Avian influenza H5N1 virus:an emerging global pandemic, in: S.K. Lai (Ed.), Emerging Viral Diseases of Southeast Asia, Karger, Basel.2007, pp.59-77.
[100]V.T. Chow, P.A. Tambyah, K.T. Goh, To kill a mocking bird flu? Ann. Acad. Med. 2008,37:451-453.
[101]R.G. Webster, K.F. Shortridge, Y. Kawaoka, Influenza:interspecies transmission and emergence of new pandemics, FEMS Immunol. Med. Microbiol.1997,18:275-279.
[102]J.C. de Jong, E.C. Claas, A.D. Osterhaus, R.G. Webster, W.L. Lim, A pandemic warning? Nature.1997,389:554-560.
[103]J.K. Taubenberger, D.M. Morens,1918 influenza:the mother of all pandemics. Emerg. Infect. Dis.2006,12:15-22.
[104]De Jong J C, Rimmelzwaan G F, Fouchier R A, Osterhaus A D. Influenza virus:a master of metamorphosis. J Infect.2000,40:218-228.
[105]Horimoto T, Kawaoka Y. Influenza:lessons from past pandemics, warnings from current incidents. Nat Rev Microbiol.2005,3:591-600.
[106]E.D. Kilbourne, In pursuit of influenza:Fort Monmouth to Valhalla (and back). Bioessays.1997, (19):641-650.
[107]A.C. Ward, Virulence of influenza A virus for mouse lung. Virus Genes.1997, (14):187-194.
[108]X. Lu, T.M. Tumpey, T. Morken, S.R. Zaki, N.J. Cox, J.M. Katz. A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. J. Virol.1999, (73):5903-5911.
[109]G.F. Rimmelzwaan, D. van Riel, M. Baars, T.M. Bestebroer, G. van Amerongen, R.A. Fouchier, A.D. Osterhaus, T. Kuiken. Influenza Avirus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am. J.Pathol.2006, (168):176-183.
[110]E.G. Brown. Increased virulence of a mouse-adapted variant of influenza A/FM/1/47 virus is controlled by mutations in genome segments 4,5,7, and 8. J. Virol.1990, (64): 4523-4533.
[111]E.G. Brown, H. Liu, L.C. Kit, S. Baird, M. Nesrallah. Pattern of mutation in the genome of influenza Avirus on adaptation to increased virulence in the mouse lung: identification of functional themes. Proc. Natl. Acad. Sci. U.S.A.2001, (98):6883-6888.
[112]C.A. Smeenk, E.G. Brown. The influenza virus variant A/FM/1/47-MA possesses single amino acid replacements in the hemagglutinin, controlling virulence, and in the matrix protein, controlling virulence as well as growth. J. Virol.1994, (68):530-534.
[113]T. Ito, Y. Suzuki, L. Mitnaul, A. Vines, H. Kida, Y. Kawaoka. Receptor specificity of influenza A viruses correlates with the agglutination of erythrocytes from different animal species. Virology.1997, (227):493-499.
[114]A. Ibricevic, A. Pekosz, M.J. Walter, C. Newby, J.T. Battaile, E.G. Brown, M.J. Holtzman, S.L. Brody. Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cells. J. Virol.2006, (80):7469-7480.
[115]J. Meisner, K.J. Szretter, K.C. Bradley, W.A. Langley, Z.N. Li, B.J. Lee, S. Thoennes, J. Martin, J.J. Skehel, R.J. Russell, J.M. Katz, D.A. Steinhauer. Infectivity studies of influenza virus hemagglutinin receptor binding site mutants in mice. J. Virol.2008, (82): 5079-5083.
[116]孙惠惠.H1N1小鼠模型的建立及板蓝根颗粒对H1N1模型小鼠的作用的研究.硕士论文.北京协和医学院,2010.
[117]E.G. Brown. Increased virulence of a mouse-adapted variant of influenza A/FM/1/47 virus is controlled by mutations in genome segments 4,5,7, and 8. J. Virol 1990, (64): 4523-4533.
[118]Y. Furuta, K. Takahashi, Y. Fukuda,et al. In vitro and in vivo activities of anti-influenza virus compound T-705.Antimicrob. agents chemother.2002, (46):977-981.
[119]Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg,1938, (27):493-497.
[120]Suzuki, Y. Sialobiology of Influenza:Molecular Mechanism of Host Range Variation of Influenza Viruses. Biological and Pharmaceutical Bulletin,2005,28,399-408.
[121]Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, Klimov A. Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology,2006,344(2), 432-438.
[122]Krug RM, Yuan W, Noah DL, et al. Intracellular warfare between human influenza viruses and human cells:the roles of the viral NS1 protein. Virology.2003,309(2):181-189.
[123]Enami M, Enami K. Characterization of influenza virus NS1 protein by using a novel helper-virus-free reverse genetic system. J Hrol,2000,74(12):5556-5561.
[124]Chien C, Tejem R, Huang Y, et al. A novel RNA-binding motif in influenza A virus non-structural protein. Nat Strttct Biol,1997,4 (11):891-895.
[125]Liu J, Lynch, PA, Chien C, et al. Crystal structure of the unique multifunctional RNA binding domain of the influenza virus NS1 protein. Nat Strttct BIO,1997,4(11):896-899.
[126]Idoia B, Tomas A, Juan O, et al. PABPI and eIF4GI associate with influenza virus NSI protein in viral mRN A translation initiation complexes. Journal of General Virology, 2003,84(12):3263-3274.
[127]Falc6n AM, MaTi6n RM, ZOrcher TZ, et al. Defective RNA replication and late gene expression in temperature-sensitive Influenza viruses expressing deleted forms of the NS1 protein. Virol,2004,78(8):3880-3888.
[128]Bomholdt ZA, Prazad BV. X-ray structure of influenza virus NS1 effactor domain. Nat Stn Mol BIof,2006,13(6):559-560.
[129]Obenauer JC, Denson J, Perdeep K. Large-Scale sequence analysis of avian influenza isolates. Science,2006,311(5767):1576-1580.
[130]张丹桂,李卫中,王革非,等.A型流感病毒NS1蛋白羧基端PL结构域影响NS1在细胞核内的定位[J].生物化学与生物物理进展,2010,37(9)：975-982.
[131]Falc6n A, Fortes P, MaTi6n RM, et al. Interaction of influenza virus NSI protein and the human homologue of Staufen in vivo and in vitro. Nucleic Acids Res,1999,7(11):2241-2247.
[132]Thomas A, Susana de la Luna, Isabel N, et al. Eukaryotic translation initiation factor 4GI is a cellular target for NS 1 protein, a translational activator of influenza virus. Molecular and Cellular Biology,2000,20(17):6259-6268.
[133]Wolf T, O'Neil R E, Palese P. Interaction cloning of NS1-I, a human protein that binds to the nonstructural NS1 proteins of influenza A and B viruses. J Virol,1996,70(8): 5363-5372.
[134]张玲,尚立霞,单卫华,等.金银花提取工艺研究[J].中药新药与临床药理,2003,14(1)：59-61.
[135]丁利君,吴振辉,蔡创海,等.金银花中黄酮类物质最佳提取工艺的研究[J].食品科学,2002,23(2)：62-65.
[136]胡克杰,孙考祥,王璐,等.绿原酸体外抗病毒作用研究[J].哈尔滨医科大学学报,2001,35(6)：430-432.
[137]王发国,叶华谷,马其侠,等.金银花及其药理作用[J].生物学通报,2004,39(5)：17-18.
[138]M. Nose, et al. Structural transformation of lignan compounds in rat gastrointestinal tract [J]. Planta Med.1992,58(6):520-523.
[139]Yao X J, Mark A, et al. Mechanism of inhibition of HIV-1 infection in vitro by purified extract of prunella vulgaris[J]. Virology.1992,187:56-58.
[140]高洋,等.牛蒡苷元体外抗流感病毒活性[J].中草药.2002,33(8)：724-726.
[141]高阳,董雪,康廷国,等.牛蒡子苷元体外抗流感病毒活性[J].中草药,2002,33(8)：724-726.
[142]杨子峰,刘妮,黄碧松,等.牛蒡苷元体内抗甲I型流感病毒作用的研究[J].中草药,2005,28(11)：1012-1014.
[143]Hisami W, Chikako M, Masahiko M, et al. Therapeutic effects of glycyrrhizin in mice infected with LP-BM5 murineretro virus and mechanisms involved in the prevention of disease progression[J]. Biotherapy,1996,9(4):209-220.
[144]Shigeyoshi H, Toshiro M, Eiji H, et al. Biochemical characterization of recombinant HIV-1 reverse transcriptase (rRT) as a glycyrrhizin- binding protein and t he CK-Ⅱ mediated stimulation of rRT activity potently inhibited by glycyrrhetinic acid derivative[J]. Biol Pharm Bull,1998,21(12):1282-1285.
[145]Sasaki H, Takei M, Kobayashi M, et al. Effect o f glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV-sero positive patients[J]. Pathobiology,2002-2003,70(4):229-236.
[146]陈宇萍,刘新记,刘克锋,等.复方甘草酸苷注射液治疗传染性非典型肺炎的临床观察[J].中国药房,2004,15(5)：294-295.
[147]Hoever G, Baltina L, Michaelis M, et al. Antiviral Activity of glycyrrhizin acid derivatives against SARS-corona virus [J]. J Med Chem,2005,48(4):1256-1259.
[148]Wu C Y, King K Y, Kuo C J, et al. Stable benzotriazole esters as mechanism-based inactivato rs of the severe acute respiratory syndrome 3CL protease [J]. Chemistry & Biology,2006,13(3):261-268.
[149]Matsuo K, Takenaka K, Shimomur a H, et al. Lamivudine and g lycyrrhizin for treatment of chemotherapy-induced hepatitis B virus (HBV) hepatitis in a chronic HBV carrier with non-Hodgkin lymphoma [J]. Leuk Lymphoma,2001,41 (1-2):191-195.
[150]张压西.复方甘草酸苷治疗慢性乙型肝炎的临床疗效及抗病毒作用观察[J].传染病信息,2005,18(2)：89-90.
[151]何卫东,徐秉坤.复方甘草酸苷注射液治疗带状疱疹疗效观察[J].中国药房,2004,15(11)：688-690.
[152]Arjun R, Mabalirajan U, Moumita D, et al. Glycyrrhizin alleviates experimental allergic asthma in mice [J]. International Immunopharmacology,2006,6:1468-1477.
[153]王秀琴,李洪源,刘鑫妍.甘草抗病毒有效部位(GD4)体外抑制呼吸道合胞病毒性作用的研究[J].中药材,2006,29(7)：692-694.
[154]刘舒,韩静,工绿娅.黄酮、异黄酮药物抑制肿瘤细胞增殖作用的最近进展[J].中国药学杂志,2004,39(1)：41-43.
[155]Clercq E D. Potential antivirals and antiviral strategies against SARS corona virus infections [J]. Expert Rev Anti Infect Ther,2006,4(2):291-302.
[156]Pompei R, Pag hi L, Ing ianni A, et al. Glycyrrhizic acid inhibits influenza virus growth in embryonated eggs[J]. Microbiologica,1983,6(3):247-250.
[157]Utsunomiya T, Kobay ashi M, Pollard R B, et al. Glycyrrhizin, an active component of licorice roots, r educes morbidity and mortability of mice infected wit h lethal dose of influenza v irus [J]. Antimicrob Agents Chemo ther,1997,41 (3):551.
[158]刘汉清,刘嘉.中药冻干制剂相关技术应用研究概药[C].中华中医药学会第九届制剂学术研讨会论文汇编.长春.中国.2008.
[159]de Clercq E. Antiviral drugs in current clinical use[J]. Journal of Clinical Virology, 2004,30(2):115.
[160]Ilyushina N A, Elena A, Govorkova, et al. Detection of amantadine-resistant variants among avian influenza viruses isolated in North America and Asia[J]. Virology,2005, 341(1):102.
[161]龚震宇,杨小平.2009年甲型流感(H1N1)大流行病毒对达菲的耐药情况[J].疾病监测,2009,24(12)：983.
[162]Chen J X, Xue H J, Ye W C, et al. Activity of Andrographolide and Its Derivatives against Influenza Virus in Vivo and in Vitro[J]. Biol Pharm Bull,2009,32(8):1385.
[163]Ehrhardt,C,Hrincius,ERIKorte,V. CYSTUS052, exerts anti influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance. Antiviral Research.2007,76(1):38.
[164]Reed LJ, Muench H. A simple method of estimating fifty percent endpoints[J]. Am J Hyg,1938,27:493.
[165]R. Ian Freshney. Animal Cell Culture, a Practical approach[M]. Oxford University Press,1992.361
[166]Knox YM, Suzutani T, Yosida I, et al. Anti-influenza virus activity of crude extract of Ribes nigrum L[J].Phytother Res.2003; 17(2):120.
[167]Y Furuta, K Takahashi, Y Fukuda, et al. In vitro and in vivo activities of anti-influenza virus compound T-705[J].Antimicrob Agents Chemother.2002; 46 (4):977.
[168]刘崇海,皮光环,王莉佳,等.噻唑蓝(MTT)法空斑形成实验在病毒检测中的应用[J].川北医学院学报,2010,25(6)：509-512.
[169]徐淑云,卞如濂,陈修.药理实验方法学[M].3版.北京：人民卫生出版社,2001.226-234,1720-1740.9(专著)
[170]Szapiel SV, Elson NA, Fulmer TD, et al. Bleomycin2induced in2 terstitial pulmonary disease in the Nude, Athymic mouse [J]. Am Rev Respir Dis,1979, 120:8932899.
[171]Y. Furuta, K. Takahashi, Y. Fukuda,et al.In vitro and in vivo activities of anti-influenza virus compound T-705.Antimicrob [J]. agents chemother.2002; 46 (4): 977-81.
[172]Reed LJ, Muench H. A simple method of estimating fifty percent endpoints [J]. Am J Hyg,1938,27(3):493-497.
[173]罗凤岩,王淑梅.银翘散临床应用概述[JJ.现代中西医结合杂志,2009,18(30)：3781-3783.
[174]白刚.中药方剂研究与应用大全[M].北京：中国科学技术出版社,1995：972.
[175]何建萍.银翘散的临床药理[J].中]国实用医药,2009,4(23)：149-150.
[176]刘亚娴,霍炳杰,张莉,刘羽,李晶.银翘散在不同煎煮时间下对免疫抑制小鼠的免疫调节作用[J].中医杂志,2008,49(12)：1112-1115.
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