Peut Viv, Kent Stephen J
Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia.
J Virol. 2007 Dec;81(23):13125-34. doi: 10.1128/JVI.01408-07. Epub 2007 Sep 26.
Human immunodeficiency virus (HIV)-specific CD8 T lymphocytes are important for the control of viremia, but the relative utility of responses to the various HIV proteins is controversial. Immune responses that force escape mutations that exact a significant fitness cost from the mutating virus would help slow progression to AIDS. The HIV envelope (Env) protein is subject to both humoral and cellular immune responses, suggesting that multiple rounds of mutation are needed to facilitate viral escape. The Gag protein, however, has recently been shown to elicit a more effective CD8 T-cell immune response in humans. We studied 30 pigtail macaques for their CD8 T-lymphocyte responses to HIV-1 Env and simian immunodeficiency virus (SIV) Gag following prime/boost vaccination and intrarectal challenge with simian-human immunodeficiency virus SHIV(mn229). Eight CD8 Env-specific T-cell epitopes were identified and mapped in 10 animals. Animals that generated Env-specific CD8 T-cell responses had equivalent viral loads and only a modest advantage in retention of peripheral CD4 T lymphocytes compared to those animals without responses to Env. This contrasts with animals that generated CD8 T-cell responses to SIV Gag in the same trial, demonstrating superior control of viral load and a larger advantage in retention of peripheral CD4 T cells than Gag nonresponders. Mutational escape was common in Env but, in contrast to mutations in Gag, did not result in the rapid emergence of dominant escape motifs, suggesting modest selective pressure from Env-specific T cells. These results suggest that Env may have limited utility as a CD8 T-cell immunogen.
人类免疫缺陷病毒（HIV）特异性CD8 T淋巴细胞对于控制病毒血症很重要，但针对各种HIV蛋白的免疫反应的相对效用存在争议。迫使突变病毒付出巨大适应性代价的逃逸突变的免疫反应将有助于减缓向艾滋病的进展。HIV包膜（Env）蛋白会受到体液免疫和细胞免疫反应的影响，这表明需要多轮突变才能促进病毒逃逸。然而，最近研究表明，Gag蛋白在人类中能引发更有效的CD8 T细胞免疫反应。我们研究了30只猪尾猕猴在初次免疫/加强免疫接种以及经直肠感染猿猴-人类免疫缺陷病毒SHIV（mn229）后，其对HIV-1 Env和猿猴免疫缺陷病毒（SIV）Gag的CD8 T淋巴细胞反应。在10只动物中鉴定并定位了8个Env特异性CD8 T细胞表位。产生Env特异性CD8 T细胞反应的动物与未对Env产生反应的动物相比，病毒载量相当，仅在保留外周血CD4 T淋巴细胞方面有适度优势。这与在同一试验中对SIV Gag产生CD8 T细胞反应的动物形成对比，这些动物显示出对病毒载量的更好控制，并且在保留外周血CD4 T细胞方面比未对Gag产生反应的动物有更大优势。Env中常见突变逃逸，但与Gag中的突变不同，不会导致优势逃逸基序迅速出现，这表明Env特异性T细胞的选择压力较小。这些结果表明，Env作为CD8 T细胞免疫原的效用可能有限。
