Human Immunodeficiency Virus Type 1 Population Genetics and Adaptation in Newly Infected Individuals
Human Immunodeficiency Virus Type 1 Population Genetics and Adaptation in Newly Infected Individuals
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DOI：
10.1128/jvi.01960-08
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发表时间：
2009-03-15
影响因子：
5.4
通讯作者：
Palmer, S.
中科院分区：
文献类型：
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作者：
Kearney, M.;Maldarelli, F.;Palmer, S.
对 1 型人类免疫缺陷病毒 (HIV-1) 多样性的研究对于了解病毒发病机制、免疫逃逸变异的出现以及疫苗策略的设计至关重要。为了研究 HIV-1 群体遗传学，我们使用单基因组测序从 14 名急性感染或近期感染患者的纵向样本 (n = 93) 中获取 pro-pol 和 env 序列。 12/14 名患者感染后的第一个可用样本显示，HIV-1 群体遗传多样性较低，与单一变体的传播或生长一致。相比之下，两名患者在非反应性酶联免疫吸附测定或不确定的蛋白质印迹几天后收集的样本中显示出不同病毒群体的高度多样性和共存，这与多种变体的传播或生长一致。对所有患者的第一个样本的 PR 和 RT 序列与共有 B 亚组序列进行比较表明，几乎所有非同义差异都仅限于已识别的细胞毒性 T 淋巴细胞 (CTL) 表位。对于 HLA 型患者，与传播变异体中的共识相比，在患者的主要组织相容性复合体类型无法识别的表位中发现了突变。在研究期间（最长 5 年）很少见到传播突变的逆转。这些数据表明，急性B亚型HIV-1感染通常是由携带CTL表位突变的单一病毒变体的传播或生长引起的，这些CTL表位是在供体或先前供体中传播之前选择的，并且这些突变的逆转可能非常缓慢。这些结果对疫苗策略具有重要意义，因为它们意味着一些 HLA 等位基因可能在新获得的 HIV 感染中受到损害。
Studies on human immunodeficiency virus type 1 (HIV-1) diversity are critical for understanding viral pathogenesis and the emergence of immune escape variants and for design of vaccine strategies. To investigate HIV-1 population genetics, we used single-genome sequencing to obtain pro-pol and env sequences from longitudinal samples (n = 93) from 14 acutely or recently infected patients. The first available sample after infection for 12/14 patients revealed HIV-1 populations with low genetic diversity, consistent with transmission or outgrowth of a single variant. In contrast, two patients showed high diversity and coexistence of distinct virus populations in samples collected days after a nonreactive enzyme-linked immunosorbent assay or indeterminate Western blot, consistent with transmission or outgrowth of multiple variants. Comparison of PR and RT sequences from the first sample for all patients with the consensus subgroup B sequence revealed that nearly all nonsynonymous differences were confined to identified cytotoxic T-lymphocyte (CTL) epitopes. For HLA-typed patients, mutations compared to the consensus in transmitted variants were found in epitopes that would not be recognized by the patient's major histocompatibility complex type. Reversion of transmitted mutations was rarely seen over the study interval (up to 5 years). These data indicate that acute subtype B HIV-1 infection usually results from transmission or outgrowth of single viral variants carrying mutations in CTL epitopes that were selected prior to transmission either in the donor or in a previous donor and that reversion of these mutations can be very slow. These results have important implications for vaccine strategies because they imply that some HLA alleles could be compromised in newly acquired HIV infections.