Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
PLoS One. 2013 May 6;8(5):e61383. doi: 10.1371/journal.pone.0061383. Print 2013.
CD8+ T Lymphocytes (CTL) can control AIDS virus replication. However, natural selection favoring viral variants that escape CTL recognition is a common feature of both simian immunodeficiency virus (SIV) infection of macaques and HIV infection of humans. Emerging data indicate that CTL directed against alternate reading frame (ARF)-derived epitopes (a.k.a. cryptic epitopes) are important components of the total virus-specific response in SIV and HIV infection but the contributions of these responses during the critical first several weeks of infection have not been determined. We used a focused deep sequencing approach to examine acute phase viral evolution in response to CTL targeting two polypeptides encoded by ARFs of SIVmac239 in SIV-infected rhesus macaques. We report high magnitude CTL responses as early as three weeks post-infection against epitopes within both ARFs, which both overlap the 5' end of the env gene. Further, mutations accumulated in the epitopes by three to four weeks post infection consistent with viral escape. Interestingly, these mutations largely maintained the primary amino acid sequence of the overlapping Envelope protein. Our data show that high frequency CTL target cryptic epitopes and exert selective pressure on SIV during the acute phase, underscoring the importance of these unique immune responses.
CD8+ T 淋巴细胞（CTL）可以控制艾滋病病毒的复制。然而，有利于病毒变异体逃避 CTL 识别的自然选择是猴免疫缺陷病毒（SIV）感染猕猴和人类感染 HIV 的共同特征。新出现的数据表明，针对交替阅读框（ARF）衍生表位（又称隐匿表位）的 CTL 是 SIV 和 HIV 感染中总病毒特异性反应的重要组成部分，但这些反应在感染的最初几周内的贡献尚未确定。我们使用了一种集中的深度测序方法来研究针对 SIVmac239 的 ARF 编码的两种多肽的 CTL 靶向反应在 SIV 感染的恒河猴中的急性阶段病毒进化。我们报告了在感染后三到四周内针对两个 ARF 内的表位的高幅度 CTL 反应，这些表位都重叠了 env 基因的 5'端。此外，在感染后三到四周内，表位中积累的突变与病毒逃逸一致。有趣的是，这些突变在很大程度上保持了重叠的 Envelope 蛋白的主要氨基酸序列。我们的数据表明，高频率的 CTL 靶向隐匿表位，并在急性阶段对 SIV 施加选择压力，强调了这些独特的免疫反应的重要性。
