Immunologic pressure within class I-restricted cognate human immunodeficiency virus epitopes during highly active antiretroviral therapy
Immunologic pressure within class I-restricted cognate human immunodeficiency virus epitopes during highly active antiretroviral therapy
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DOI：
10.1128/jvi.79.6.3653-3663.2005
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发表时间：
2005-03-01
影响因子：
5.4
通讯作者：
Koup, RA
中科院分区：
文献类型：
--
作者：
Casazza, JP;Betts, MR;Koup, RA
细胞毒性T淋巴细胞（CTL）和高效抗逆转录病毒疗法（HAART）在人类免疫缺陷病毒（HIV）感染过程中对病毒群体施加强大的进化压力。然而，尚不清楚CTL应答是否在治疗期间继续实质性地影响病毒进化。为了研究HAART期间免疫压力对病毒序列的影响，我们在5名未经治疗的患者中确定了10个靶向HIV特异性CD 8（+）-T细胞表位，对血浆衍生病毒中的每个表位进行测序，然后通过比较血浆中病毒变异体的频率与对每个变异体的CD 8（+）-T细胞应答频率来确定这些表位的免疫压力证据。对于五名患者中的一名，在治疗期间发现了病毒进化的证据。CTL靶向表位的序列从治疗开始前的明显逃逸变体变为治疗开始后CTL应答最佳识别的序列，然后在继续治疗期间最终变为新的逃逸变体。这些数据表明，CTL介导的压力可以继续影响HAART启动后的病毒进化，即使当治疗驱动病毒载量低于可检测的水平，并表明抗逆转录病毒治疗可能会优先抑制那些逃避CTL反应的病毒变异体。
Cytotoxic T lymphocytes (CTL) and highly active antiretroviral therapy (HAART) are known to exert strong evolutionary pressures on the virus population during human immunodeficiency virus (HIV) infection. However, it is not known whether CTL responses continue to substantially affect viral evolution during treatment. To study the effect of immunologic pressure on viral sequences during HAART, we identified 10 targeted HIV-specific CD8(+)-T-cell epitopes in five treatment-naive patients, sequenced each epitope in plasma-derived viruses, and then identified evidence of immunologic pressure at these epitopes by comparing the frequency of viral variants in plasma to the frequency of the CD8(+)-T-cell response for each variant identified. For one of the five patients, evidence of viral evolution was found during therapy. The sequence of the CTL-targeted epitope changed from an apparent escape variant prior to the initiation of therapy, to the sequence that is best recognized by the CTL response after the initiation of therapy, and then finally to a new escape variant during continued therapy. These data show that CTL-mediated pressure can continue to affect viral evolution after the initiation of HAART, even when treatment drives the viral load below detectable levels, and suggest that antiretroviral therapy may preferentially inhibit those virus variants that escape the CTL response.