GENETIC DIVERSITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 - EVIDENCE FOR DISTINCT SEQUENCE SUBTYPES WITH DIFFERENCES IN VIRUS BIOLOGY
GENETIC DIVERSITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 - EVIDENCE FOR DISTINCT SEQUENCE SUBTYPES WITH DIFFERENCES IN VIRUS BIOLOGY
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DOI：
10.1128/jvi.68.11.7433-7447.1994
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发表时间：
1994-11-01
影响因子：
5.4
通讯作者：
HAHN, BH
中科院分区：
文献类型：
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作者：
GAO, F;YUE, L;HAHN, BH
已知人类免疫缺陷病毒2型（HIV-2）的毒力特性差异很大，其范围从某些个体的相对减弱到另一些个体的高致病性。这些临床表现的差异，至少部分是由感染病毒株之间的遗传差异决定的。因此，全面评估HIV-2遗传多样性是了解其分子流行病学、感染自然史和生物多样性的必要的第一步。在这项研究中，我们使用巢式PCR技术从12名HIV-2血清反应性患者的未培养外周血单个核细胞的DNA中扩增病毒序列。对四个不重叠的基因组区域进行序列分析，可以全面分析HIV-2的系统发育。结果显示：(1)HIV-2存在5个不同且距离大致相等的进化谱系，与HIV-1相似，被称为序列亚型A到E；（二）艾滋病毒-2基因组嵌合的证据，表明在艾滋病毒-2感染的个体中可能发生与遗传差异菌株的共同感染和重组；（iii）支持以下结论的证据，即某些HIV-2亚型可能是由遗传多样性的黑白眉猴病毒独立引入人类群体而产生的。重要的是，只有一小部分HIV-2病毒株在培养物中复制：所有的a亚型病毒都生长到高滴度，但试图分离C、D和E亚型的代表以及大多数B亚型病毒，仍然不成功。尽管gag、pol和env区域的亚型序列差异高达25%，但所有五种病毒亚型的感染均可通过市售的血清学（Western免疫印迹）检测到。这些结果表明，HIV-2的遗传和生物多样性远比以前所认识到的要大，并表明病毒生物学中可能存在亚型特异性差异。需要系统的自然历史研究来确定这种异质性是否具有临床相关性，以及各种HIV-2亚型在体内致病性是否存在差异。
The virulence properties of human immunodeficiency virus type 2 (HIV-2) are known to vary significantly and to range from relative attenuation in certain individuals to high level pathogenicity in others. These differences in clinical manifestations may, at least in part, be determined by genetic differences among infecting virus strains. Evaluation of the full spectrum of HIV-2 genetic diversity is thus a necessary first step towards understanding its molecular epidemiology, natural history of infection, and biological diversity. In this study, we have used nested PCR techniques to amplify viral sequences from the DNA of uncultured peripheral blood mononuclear cells from 12 patients with HIV-2 seroreactivity. Sequence analysis of four nonoverlapping genomic regions allowed a comprehensive analysis of HIV-2 phylogeny. The results revealed (i) the existence of five distinct and roughly equidistant evolutionary lineages of HIV-2 which, by analogy with HIV-1, have been termed sequence subtypes A to E; (ii) evidence for a mosaic HIV-2 genome, indicating that coinfection with genetically divergent strains and recombination can occur in HIV-2-infected individuals; and (iii) evidence supporting the conclusion that some of the HIV-2 subtypes may have arisen from independent introductions of genetically diverse sooty mangabey viruses into the human population. Importantly, only a subset of HIV-2 strains replicated in culture: all subtype A viruses grew to high titers, but attempts to isolate representatives of subtypes C, D, and E, as well as the majority of subtype B viruses, remained unsuccessful. Infection with all five viral subtypes was detectable by commercially available serological (Western immunoblot) assays, despite intersubtype sequence differences of up to 25% in the gag, pol, and env regions. These results indicate that the genetic and biological diversity of HIV-2 is far greater than previously appreciated and suggest that there may be subtype-specific differences in virus biology. Systematic natural history studies are needed to determine whether this heterogeneity has clinical relevance and whether the various HIV-2 subtypes differ in their in vivo pathogenicity.