Allen T M, O'Connor D H, Jing P, Dzuris J L, Mothé B R, Vogel T U, Dunphy E, Liebl M E, Emerson C, Wilson N, Kunstman K J, Wang X, Allison D B, Hughes A L, Desrosiers R C, Altman J D, Wolinsky S M, Sette A, Watkins D I
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison 53715-1299, USA.
Nature. 2000 Sep 21;407(6802):386-90. doi: 10.1038/35030124.
Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as strong cellular immune responses develop. Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection, the data have been controversial. Here we show that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection. We sequenced the entire virus immediately after the acute phase, and found that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in controlling wild-type virus replication, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development.
人类免疫缺陷病毒（HIV）和猴免疫缺陷病毒（SIV）感染的特征是病毒血症早期出现高峰，随着强大的细胞免疫反应的发展而下降。尽管已经表明病毒特异性CD8阳性细胞毒性T淋巴细胞（CTL）在HIV和SIV感染期间施加选择性压力，但数据一直存在争议。在这里，我们表明Tat特异性CD8阳性T淋巴细胞反应在感染急性期选择新的病毒逃逸变体。我们在急性期后立即对整个病毒进行测序，发现氨基酸替换主要积累在Tat CTL表位中。这意味着Tat特异性CTL可能在控制野生型病毒复制中起重要作用，并表明针对病毒生命周期早期表达的病毒蛋白的反应可能是HIV疫苗开发的有吸引力的靶点。
