HIV-1准种传播的选择性与免疫学表位以及细胞嗜性的关系研究
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摘要
获得性免疫缺陷综合征,即艾滋病(acquired immunodeficiency syndrome, AIDS),是由人类免疫缺陷病毒(human immunodeficiency virus, HIV)感染引起的一种免疫缺陷性疾病。到2007年底,全球现有3 300多万人HIV感染者,2007年死于艾滋病的人数达210万,我国现存HIV感染者约70万人,2007年死于艾滋病的人数达2万余。因此,艾滋病是危害我国,乃至全世界的重要传染病之一。
母婴传播和性传播是HIV-1的2种重要的传播方式,也是目前HIV-1感染迅速增长的主要原因之一。研究发现,HIV-1传播受多种因素影响,如感染途径、病毒亚型、黏膜完整性以及病毒适应性等。其中对病毒囊膜可变区的研究最多,因为病毒囊膜蛋白gp120亚单位不但能够决定病毒的细胞嗜性,而且是中和抗体的主要作用靶点。此外,研究HIV-1的env基因的多样性可以在一定程度上反映整个基因组的情况。
HIV-1传播的遗传“瓶颈”效应越来越受到人们关注,相关的研究也层出不穷。目前的研究结果显示,母婴传播与性传播在选择性压力方面存在不同的机制,中和抗体的筛选作用在母婴传播中较为突出,而中和抗体在性传播中的筛选作用不明显,完整的黏膜对性传播的选择起关键作用。HIV-1的细胞嗜性在传播中也是重要的选择因素,既往的研究发现,发生传播的绝对多数均为R5巨噬细胞嗜性的HIV-1。已知CTL在HIV-1感染中起重要作用,其发挥作用是通过与HLA限制性的CTL表位结合识别并杀伤靶细胞。CTL是否也在传播中起选择作用,目前尚未见到相关研究报道。理论上讲,更换宿主后,HLA类型不同,CTL作用表位必然不同,推测其在传播中有一定的选择作用。
目前发现的HIV-1的CTL表位有很多,几乎所有HIV-1编码的蛋白上均有CTL的表位。因此,HIV-1各个区域相应位点的突变均可导致CTL表位的改变。HIV-1各个区域突变频率不同,env区突变频率最高,导致的CTL表位变化最多。
HIV-1感染后可刺激机体产生针对囊膜蛋白的中和抗体。艾滋病病人体内中和抗体滴度水平明显较无症状携带者低,说明中和抗体有一定的保护作用。但抗体不能与单核巨噬细胞内存留的病毒接触,且HIV-1囊膜蛋白易发生抗原性变异,使原有中和抗体不能发挥应有的作用。此外,在潜伏感染阶段,HIV前病毒整合入宿主细胞基因组中,不被免疫系统识别,也是逃避免疫清除的一种方式。囊膜蛋白是中和抗体的主要靶点,其中gp120的V3区的顶端4肽是重要的免疫优势中和结构域(principal neutralizing epitope, PND)。
鉴于以上理论,我们设计并实施如下研究方案:从109例HIV感染者中挑选4对母婴传播和8对男传女性传播的传播者和感染者作为研究对象,分析传播者和感染者体内HIV-1准种复杂度和熵值,对该区域进行序列分析,确定病毒的细胞嗜性,寻找存在的CTL表位和中和抗体表位,探究在两种传播方式下,病毒准种传播的选择性与CTL表位、中和抗体表位和细胞嗜性的变化的关系,为进一步揭示传播的遗传“瓶颈”效应提供实验依据。
主要研究结果
1.分析并总结了1995年11月至2008年1月,确诊艾滋病患者及感染HIV的配偶或/和子女共109例的流行病学和临床资料,其中包括4对母婴传播病例和8对男传女性传播病例。流行病学分析:109例中男性有64例,女性45例,21岁～40岁间有67例,来自重庆市的有77例,性传播感染者有64例;临床表现:最常见的3个临床表现为发热(60例)、体重减轻(46例)和腹泻(15例);检查结果:CD4细胞计数结果的最大值为670个/μl,最小值为2个/μl,平均值为120.35±82.83个/μl;HIV-RNA的最大值为5.222×10~7copies/ml,最小值为0 copy/ml,平均值为6.56×10~4copies/ml;治疗及预后:有15例接受HAART,2例在治疗过程中死亡,其余13例健在。
2.母婴传播病例的病毒准种复杂度和熵值分析结果:4对中有3对的母亲的病毒准种复杂度和熵值高于其子,只有1对的母亲低于其子;母婴传播病例的CTL表位分析结果:2对子代体内病毒出现母亲没有的新表位,另外2对未出现新表位;中和抗体表位分析发现:仅发现2个次要中和抗体表位;未发现含顶端4肽的主要中和表位;细胞嗜性预测结果:其中2对母子体内的病毒均为R5型、非合胞体诱导型、巨噬细胞嗜性,1对为X4型、合胞体诱导型、T细胞嗜性,1对的母亲为R5、非合胞体诱导型、巨噬细胞嗜性,其子为X4型、合胞体诱导型、T细胞嗜性。
3.性传播病例的病毒准种复杂度和熵值分析结果:8对中有4对的男性体内病毒准种复杂度和熵值高于女性,有3对的男性低于女性,1对男女相同;CTL表位分析结果:5对被传播感染的女性出现了传播者男性没有的新表位,其余3对未出现新表位;中和抗体表位分析发现:发现2个中和抗体表位,一个是次要中和抗体表位,另一个是主要中和抗体表位“IGPGR”,仅一例传播者体内病毒含此表位;细胞嗜性预测结果:其中5对均为R5型、非合胞体诱导型、巨噬细胞嗜性,2对为X4、合胞体诱导型、T细胞嗜性,1对的男性为X4型、合胞体诱导型、T细胞嗜性,女性为R5型、非合胞体诱导型、巨噬细胞嗜性。
结论
1.通过我院13年109例HIV感染者资料系统综合分析提出对本地区病例的以下新认识:
(1)艾滋病已经从既往的少见病逐渐成为常见病,性传播途径感染比例最高,感染者以中青年为主,女性感染人数不断增加。
(2)最常见的临床表现复杂,常见病的表现不典型,少见病容易造成误诊或漏诊。
(3)艾滋病并发症能够被有效控制,联合HAART可明显提高生活质量和延长生存时间。
2.通过四对母婴传播有关研究结果系统综合分析有以下新发现:
(1)母亲的准种复杂度和熵值通常高于其子,说明准种传播的选择性存在。
(2)被选择性传播的HIV-1准种可快速进化产生新的CTL表位,随着时间的延长,产生的新的CTL表位的概率增高。
(3)被选择性传播的HIV-1准种对中和抗体有抗性,且为巨噬细胞嗜性。
3.通过八对性传播有关研究结果系统综合分析有以下新发现:
(1)传播者的准种复杂度和熵值高于被传播者,说明准种传播的选择性存在。
(2)被选择性传播的HIV-1准种可快速进化产生新的CTL表位。
(3)被选择性传播的HIV-1准种为巨噬细胞嗜性。
AIDS is a disease of the human immune system that is characterized by reduction in the numbers of CD4-bearing helper T cells to 20 percent or less of normal thereby rendering the subject highly vulnerable to life-threatening conditions and that is caused by infection with HIV commonly transmitted in infected blood and bodily secretions. The estimated number of people living with HIV was 33.2 million worldwide in 2007, consisting of adults 30.7 million and 2.5 million children under 15 years and the estimated number of AIDS death was 2.1 million in 2007. In china, 223 501 HIV positives cases had been reported, including 62 838 AIDS cases and 22 205 death cases by the end of October 2007. So AIDS is considered to be one of the most threatening public health problems in modern society.
HIV is classified into two types, HIV-1 and HIV-2. While HIV-1 predominates the worldwide disaster and generally when people refer to HIV without specifying the type of virus they will be referring to HIV-1. The relatively uncommon HIV-2 type is concentrated in West Africa and is rarely found elsewhere. The strains of HIV-1 can be classified into three groups, the major group M, the outlier group O and the new group N. HIV tropism refers to the cell type that the HIV infects and replicates in. M-tropic strains of HIV-1, or non-syncytium-inducing strains (NSI) use the beta-chemokine receptor CCR5 for entry and are thus able to replicate in macrophages. T-tropic isolates, or syncitium-inducing (SI) strains replicate in primary CD4+ T-cells and use the alpha-chemokine receptor, CXCR4, for entry. Viruses that use only the CCR5 receptor are termed R5, those that only use CXCR4 are termed X4, and those that use both, X4/R5.
HIV has several major genes coding for structural proteins that are found in all retroviruses, and several nonstructural ("accessory") genes that are unique to HIV. The gag gene provides the basic physical infrastructure of the virus, and pol provides the basic mechanism by which retroviruses reproduce, while the others help HIV to enter the host cell and enhance its reproduction. The envelope gene(env) encodes a glycosylated polypeptide precursor(gp160) that is processed to form the exterior envelope glycoprotein(gp120) and the transmembrance glycoprotein(gp41) which anchors the envelope complex to the virus surface. It is the viral envelope that is responsible for CD4 binding, fusion, and virus entry. V3 region of envelope gp120 determins coreceptor utilization.
Mother-to-child and heterosexual transmission contribute to drive the AIDS pandemic. Although both modes of transmission most often involve a severe reduction in viral diversity from the donor quasispecies, the selective pressures are different. Our current understanding of mother-to-child transmission is that maternal neutralizing antibody are a strong selective force, but other factors including restricted glycosylation of gp120 could also be important. For heterosexual transmission, it is not just neutralization escape variants that are transmitted, because in some settings it appears that transmission results in the selection of variants that lack resistance to the donor’s neutralizing antibodies.
We designed and conducted the experiments as follow: selecting 4 pairs of mother-to-child and 8 pairs of heterosexual transmission as objects from 109 HIV-positive cases; analysing complexity and entropy of HIV-1 quasispecies in each pair; searching possible CTL and neutralizing antibody epitopes in env region from sequencing results; predicting tropisms of HIV-1 in each pair by geno2pheno software.
The Main Research Results
1. We had collected 109 AIDS patients and their couples or children HIV-1 carriers including 4 pairs of mother-to-child transmission cases and 8 pairs of heterosexual transmission cases. The most common clinical manifestations of AIDS patients are fever, losing weight and diarrhea. The maximum of CD4 cell count of these cases is 670/μl, the minimum is 2/μl and the average is 120.35±82.83/μl; The maximum of HIV-RNA is 5.222×10~7copies/ml, the minimum is 0 copy/ml and the average is 6.56×10~4copies/ml. Fifteen cases received HAART, two died during the trerapy and thirteen were still alive and maintained symptomless.
2. Analysis results of clonotype number, quasispecies complexity and entropy of 4 mother-to-child transmission pairs were as follow, clonotype number, quasispecies complexity and entropy of mothers in 3 of 4 pairs were higher than those of their children respectively and the results in 1 pairs was opposite. Analysis results of CTL epitopes were as follow, the evolution of children’s HIV-1 in 2 of 4 pairs produced new epitopes which could not be found in their mothers’, the evolution of the children’s in the other 2 pairs produced nothing special compared to their mothers’. Analysis results of neutralizing antibody epitopes were as follow, two minor and no major neutralizing antibody epitopes were found. Predicting results of HIV-1 tropisms were as follow, two pairs of mother-to-child transmission pairs were M-tropic consistently, one pair was T-tropic consistently and the mother of the last pair was M-tropic and her child was T-tropic.
3. Analysis results of clonotype number, quasispecies complexity and entropy of 8 heterosexual transmission pairs were as follow, clonotype number, quasispecies complexity and entropy of males in 4 of 8 pairs were higher than those of their corresponding females respectively, the results in 3 pairs were opposite and the results of male and female in 1 pair were same. Analysis results of CTL epitopes of 8 heterosexual transmission pairs were as follow, the evolution of females’HIV-1 in 5 of 8 pairs produced new epitopes which could not be found in their partners’, the evolution of the females’in the other 3 pairs produced nothing special compared to their partners’. Analysis results of neutralizing antibody epitopes were as follow, one minor and major neutralizing antibody epitope were found. Predicting results of HIV-1 tropisms were as follow, five pairs of heterosexual transmission pairs were M-tropic consistently, two pairs were T-tropic consistently and the male of the last pair was T-tropic and the female was M-tropic.
Conclusion
1. The number of AIDS patients had been increasing since 2001. Heterosexual transmission contribute to the most HIV infected cases. Yong and middle-aged people dominate in HIV-1 infected cases and the number of infected females are increasing. The most common clinical magnifications are all helpless to the diagnosis and AIDS patients’CD4 cell counts are all below 200/μl and their viral loads are all very high( beyond 105copies/ml). Those patients’life quality can be improved and their life time can be prolonged by HAART after their complications were controlled.
2. The complexity and entropy of HIV-1 quasispecies of the mother transmitters are higher than those of the child recipients. HIV-1 usually evolutes quickly and produces new CTL epitopes after entering the child recipients. The magtitudes of HLA restricted CTL epitopes changes induced by mutated HIV-1 quasispecies after mother-to-child transmission increase as time going. M-tropic HIV-1 resistant to maternal neutralizing antibody dominates in mother-to-child transmission.
3. The complexity and entropy of HIV-1 quasispecies of the male transmitters are higher than those of the femal recipients. HIV-1 usually evolutes quickly and produces new CTL epitopes after entering the female recipients. M-tropic HIV-1 dominates in heterosexual transmission.
母婴传播和性传播是HIV-1的2种重要的传播方式,也是目前HIV-1感染迅速增长的主要原因之一。研究发现,HIV-1传播受多种因素影响,如感染途径、病毒亚型、黏膜完整性以及病毒适应性等。其中对病毒囊膜可变区的研究最多,因为病毒囊膜蛋白gp120亚单位不但能够决定病毒的细胞嗜性,而且是中和抗体的主要作用靶点。此外,研究HIV-1的env基因的多样性可以在一定程度上反映整个基因组的情况。
HIV-1传播的遗传“瓶颈”效应越来越受到人们关注,相关的研究也层出不穷。目前的研究结果显示,母婴传播与性传播在选择性压力方面存在不同的机制,中和抗体的筛选作用在母婴传播中较为突出,而中和抗体在性传播中的筛选作用不明显,完整的黏膜对性传播的选择起关键作用。HIV-1的细胞嗜性在传播中也是重要的选择因素,既往的研究发现,发生传播的绝对多数均为R5巨噬细胞嗜性的HIV-1。已知CTL在HIV-1感染中起重要作用,其发挥作用是通过与HLA限制性的CTL表位结合识别并杀伤靶细胞。CTL是否也在传播中起选择作用,目前尚未见到相关研究报道。理论上讲,更换宿主后,HLA类型不同,CTL作用表位必然不同,推测其在传播中有一定的选择作用。
目前发现的HIV-1的CTL表位有很多,几乎所有HIV-1编码的蛋白上均有CTL的表位。因此,HIV-1各个区域相应位点的突变均可导致CTL表位的改变。HIV-1各个区域突变频率不同,env区突变频率最高,导致的CTL表位变化最多。
HIV-1感染后可刺激机体产生针对囊膜蛋白的中和抗体。艾滋病病人体内中和抗体滴度水平明显较无症状携带者低,说明中和抗体有一定的保护作用。但抗体不能与单核巨噬细胞内存留的病毒接触,且HIV-1囊膜蛋白易发生抗原性变异,使原有中和抗体不能发挥应有的作用。此外,在潜伏感染阶段,HIV前病毒整合入宿主细胞基因组中,不被免疫系统识别,也是逃避免疫清除的一种方式。囊膜蛋白是中和抗体的主要靶点,其中gp120的V3区的顶端4肽是重要的免疫优势中和结构域(principal neutralizing epitope, PND)。
鉴于以上理论,我们设计并实施如下研究方案:从109例HIV感染者中挑选4对母婴传播和8对男传女性传播的传播者和感染者作为研究对象,分析传播者和感染者体内HIV-1准种复杂度和熵值,对该区域进行序列分析,确定病毒的细胞嗜性,寻找存在的CTL表位和中和抗体表位,探究在两种传播方式下,病毒准种传播的选择性与CTL表位、中和抗体表位和细胞嗜性的变化的关系,为进一步揭示传播的遗传“瓶颈”效应提供实验依据。
主要研究结果
1.分析并总结了1995年11月至2008年1月,确诊艾滋病患者及感染HIV的配偶或/和子女共109例的流行病学和临床资料,其中包括4对母婴传播病例和8对男传女性传播病例。流行病学分析:109例中男性有64例,女性45例,21岁～40岁间有67例,来自重庆市的有77例,性传播感染者有64例;临床表现:最常见的3个临床表现为发热(60例)、体重减轻(46例)和腹泻(15例);检查结果:CD4细胞计数结果的最大值为670个/μl,最小值为2个/μl,平均值为120.35±82.83个/μl;HIV-RNA的最大值为5.222×10~7copies/ml,最小值为0 copy/ml,平均值为6.56×10~4copies/ml;治疗及预后:有15例接受HAART,2例在治疗过程中死亡,其余13例健在。
2.母婴传播病例的病毒准种复杂度和熵值分析结果:4对中有3对的母亲的病毒准种复杂度和熵值高于其子,只有1对的母亲低于其子;母婴传播病例的CTL表位分析结果:2对子代体内病毒出现母亲没有的新表位,另外2对未出现新表位;中和抗体表位分析发现:仅发现2个次要中和抗体表位;未发现含顶端4肽的主要中和表位;细胞嗜性预测结果:其中2对母子体内的病毒均为R5型、非合胞体诱导型、巨噬细胞嗜性,1对为X4型、合胞体诱导型、T细胞嗜性,1对的母亲为R5、非合胞体诱导型、巨噬细胞嗜性,其子为X4型、合胞体诱导型、T细胞嗜性。
3.性传播病例的病毒准种复杂度和熵值分析结果:8对中有4对的男性体内病毒准种复杂度和熵值高于女性,有3对的男性低于女性,1对男女相同;CTL表位分析结果:5对被传播感染的女性出现了传播者男性没有的新表位,其余3对未出现新表位;中和抗体表位分析发现:发现2个中和抗体表位,一个是次要中和抗体表位,另一个是主要中和抗体表位“IGPGR”,仅一例传播者体内病毒含此表位;细胞嗜性预测结果:其中5对均为R5型、非合胞体诱导型、巨噬细胞嗜性,2对为X4、合胞体诱导型、T细胞嗜性,1对的男性为X4型、合胞体诱导型、T细胞嗜性,女性为R5型、非合胞体诱导型、巨噬细胞嗜性。
结论
1.通过我院13年109例HIV感染者资料系统综合分析提出对本地区病例的以下新认识:
(1)艾滋病已经从既往的少见病逐渐成为常见病,性传播途径感染比例最高,感染者以中青年为主,女性感染人数不断增加。
(2)最常见的临床表现复杂,常见病的表现不典型,少见病容易造成误诊或漏诊。
(3)艾滋病并发症能够被有效控制,联合HAART可明显提高生活质量和延长生存时间。
2.通过四对母婴传播有关研究结果系统综合分析有以下新发现:
(1)母亲的准种复杂度和熵值通常高于其子,说明准种传播的选择性存在。
(2)被选择性传播的HIV-1准种可快速进化产生新的CTL表位,随着时间的延长,产生的新的CTL表位的概率增高。
(3)被选择性传播的HIV-1准种对中和抗体有抗性,且为巨噬细胞嗜性。
3.通过八对性传播有关研究结果系统综合分析有以下新发现:
(1)传播者的准种复杂度和熵值高于被传播者,说明准种传播的选择性存在。
(2)被选择性传播的HIV-1准种可快速进化产生新的CTL表位。
(3)被选择性传播的HIV-1准种为巨噬细胞嗜性。
AIDS is a disease of the human immune system that is characterized by reduction in the numbers of CD4-bearing helper T cells to 20 percent or less of normal thereby rendering the subject highly vulnerable to life-threatening conditions and that is caused by infection with HIV commonly transmitted in infected blood and bodily secretions. The estimated number of people living with HIV was 33.2 million worldwide in 2007, consisting of adults 30.7 million and 2.5 million children under 15 years and the estimated number of AIDS death was 2.1 million in 2007. In china, 223 501 HIV positives cases had been reported, including 62 838 AIDS cases and 22 205 death cases by the end of October 2007. So AIDS is considered to be one of the most threatening public health problems in modern society.
HIV is classified into two types, HIV-1 and HIV-2. While HIV-1 predominates the worldwide disaster and generally when people refer to HIV without specifying the type of virus they will be referring to HIV-1. The relatively uncommon HIV-2 type is concentrated in West Africa and is rarely found elsewhere. The strains of HIV-1 can be classified into three groups, the major group M, the outlier group O and the new group N. HIV tropism refers to the cell type that the HIV infects and replicates in. M-tropic strains of HIV-1, or non-syncytium-inducing strains (NSI) use the beta-chemokine receptor CCR5 for entry and are thus able to replicate in macrophages. T-tropic isolates, or syncitium-inducing (SI) strains replicate in primary CD4+ T-cells and use the alpha-chemokine receptor, CXCR4, for entry. Viruses that use only the CCR5 receptor are termed R5, those that only use CXCR4 are termed X4, and those that use both, X4/R5.
HIV has several major genes coding for structural proteins that are found in all retroviruses, and several nonstructural ("accessory") genes that are unique to HIV. The gag gene provides the basic physical infrastructure of the virus, and pol provides the basic mechanism by which retroviruses reproduce, while the others help HIV to enter the host cell and enhance its reproduction. The envelope gene(env) encodes a glycosylated polypeptide precursor(gp160) that is processed to form the exterior envelope glycoprotein(gp120) and the transmembrance glycoprotein(gp41) which anchors the envelope complex to the virus surface. It is the viral envelope that is responsible for CD4 binding, fusion, and virus entry. V3 region of envelope gp120 determins coreceptor utilization.
Mother-to-child and heterosexual transmission contribute to drive the AIDS pandemic. Although both modes of transmission most often involve a severe reduction in viral diversity from the donor quasispecies, the selective pressures are different. Our current understanding of mother-to-child transmission is that maternal neutralizing antibody are a strong selective force, but other factors including restricted glycosylation of gp120 could also be important. For heterosexual transmission, it is not just neutralization escape variants that are transmitted, because in some settings it appears that transmission results in the selection of variants that lack resistance to the donor’s neutralizing antibodies.
We designed and conducted the experiments as follow: selecting 4 pairs of mother-to-child and 8 pairs of heterosexual transmission as objects from 109 HIV-positive cases; analysing complexity and entropy of HIV-1 quasispecies in each pair; searching possible CTL and neutralizing antibody epitopes in env region from sequencing results; predicting tropisms of HIV-1 in each pair by geno2pheno software.
The Main Research Results
1. We had collected 109 AIDS patients and their couples or children HIV-1 carriers including 4 pairs of mother-to-child transmission cases and 8 pairs of heterosexual transmission cases. The most common clinical manifestations of AIDS patients are fever, losing weight and diarrhea. The maximum of CD4 cell count of these cases is 670/μl, the minimum is 2/μl and the average is 120.35±82.83/μl; The maximum of HIV-RNA is 5.222×10~7copies/ml, the minimum is 0 copy/ml and the average is 6.56×10~4copies/ml. Fifteen cases received HAART, two died during the trerapy and thirteen were still alive and maintained symptomless.
2. Analysis results of clonotype number, quasispecies complexity and entropy of 4 mother-to-child transmission pairs were as follow, clonotype number, quasispecies complexity and entropy of mothers in 3 of 4 pairs were higher than those of their children respectively and the results in 1 pairs was opposite. Analysis results of CTL epitopes were as follow, the evolution of children’s HIV-1 in 2 of 4 pairs produced new epitopes which could not be found in their mothers’, the evolution of the children’s in the other 2 pairs produced nothing special compared to their mothers’. Analysis results of neutralizing antibody epitopes were as follow, two minor and no major neutralizing antibody epitopes were found. Predicting results of HIV-1 tropisms were as follow, two pairs of mother-to-child transmission pairs were M-tropic consistently, one pair was T-tropic consistently and the mother of the last pair was M-tropic and her child was T-tropic.
3. Analysis results of clonotype number, quasispecies complexity and entropy of 8 heterosexual transmission pairs were as follow, clonotype number, quasispecies complexity and entropy of males in 4 of 8 pairs were higher than those of their corresponding females respectively, the results in 3 pairs were opposite and the results of male and female in 1 pair were same. Analysis results of CTL epitopes of 8 heterosexual transmission pairs were as follow, the evolution of females’HIV-1 in 5 of 8 pairs produced new epitopes which could not be found in their partners’, the evolution of the females’in the other 3 pairs produced nothing special compared to their partners’. Analysis results of neutralizing antibody epitopes were as follow, one minor and major neutralizing antibody epitope were found. Predicting results of HIV-1 tropisms were as follow, five pairs of heterosexual transmission pairs were M-tropic consistently, two pairs were T-tropic consistently and the male of the last pair was T-tropic and the female was M-tropic.
Conclusion
1. The number of AIDS patients had been increasing since 2001. Heterosexual transmission contribute to the most HIV infected cases. Yong and middle-aged people dominate in HIV-1 infected cases and the number of infected females are increasing. The most common clinical magnifications are all helpless to the diagnosis and AIDS patients’CD4 cell counts are all below 200/μl and their viral loads are all very high( beyond 105copies/ml). Those patients’life quality can be improved and their life time can be prolonged by HAART after their complications were controlled.
2. The complexity and entropy of HIV-1 quasispecies of the mother transmitters are higher than those of the child recipients. HIV-1 usually evolutes quickly and produces new CTL epitopes after entering the child recipients. The magtitudes of HLA restricted CTL epitopes changes induced by mutated HIV-1 quasispecies after mother-to-child transmission increase as time going. M-tropic HIV-1 resistant to maternal neutralizing antibody dominates in mother-to-child transmission.
3. The complexity and entropy of HIV-1 quasispecies of the male transmitters are higher than those of the femal recipients. HIV-1 usually evolutes quickly and produces new CTL epitopes after entering the female recipients. M-tropic HIV-1 dominates in heterosexual transmission.
引文
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5 Dickover RE, Garratty EM, Plaeger S, et al. Perinatal transmission of major, minor, and multiple maternal human immunodeficiency virus type 1 variants in utero and intrapartum. J Virol, 2001, 75:2194-2203.
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