Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1
Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1
复制标题
DOI：
10.1016/j.cell.2006.04.033
复制
发表时间：
2006-06-16
期刊：
影响因子：
64.5
通讯作者：
Kirchhoff, Frank
中科院分区：
文献类型：
--
作者：
Schindler, Michael;Muench, Jan;Kirchhoff, Frank
高水平的免疫激活和T细胞凋亡代表了HIV-1感染的标志，这在自然灵长类宿主的非致病性SIV感染中是不存在的。引起这些不同水平的免疫激活的机制尚不清楚。在这里，我们报道了来自绝大多数灵长类慢病毒（包括HIV-2）的nef等位基因下调了来自感染T细胞的TCR-CD 3，从而阻断了它们对激活的反应。相比之下，来自HIV-1和密切相关的SIV亚组的nef等位基因不能下调TCR-CD 3并抑制细胞死亡。因此，Nef介导的T细胞活化抑制是灵长类慢病毒的基本特性;其可能进化为在完整宿主免疫系统的背景下维持病毒持久性。这种功能在病毒进化过程中丧失，导致了HIV-1的产生，并可能使HIV-1的猿猴前体在人类中具有更大的致病性。
High-level immune activation and T cell apoptosis represent a hallmark of HIV-1 infection that is absent from nonpathogenic SIV infections in natural primate hosts. The mechanisms causing these varying levels of immune activation are not understood. Here, we report that nef alleles from the great majority of primate lentiviruses, including HIV-2, downmodulate TCR-CD3 from infected T cells, thereby blocking their responsiveness to activation. In contrast, nef alleles from HIV-1 and a subset of closely related SIVs fail to downregulate TCR-CD3 and to inhibit cell death. Thus, Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses; that likely evolved to maintain viral persistence in the context of an intact host immune system. This function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans.