Differential incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and major histocompatibility complex class I and II molecules into human immunodeficiency virus type 1 virions and microvesicles: implications for viral pathogenesis and immune regulation
Differential incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and major histocompatibility complex class I and II molecules into human immunodeficiency virus type 1 virions and microvesicles: implications for viral pathogenesis and immune regulation
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DOI：
10.1128/jvi.75.13.6173-6182.2001
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发表时间：
2001-07-01
影响因子：
5.4
通讯作者：
Lifson, JD
中科院分区：
文献类型：
--
作者：
Esser, MT;Graham, DR;Lifson, JD
人类免疫缺陷病毒（HIV）感染导致CD 4（+）T细胞功能受损，早在循环CD 4（+）T细胞数量明显下降之前。导致这种功能性无反应性和CD 4（+）T细胞最终耗竭的机制仍不清楚。CD 4+细胞的致细胞病变感染的直接作用和未感染的“旁观者”细胞功能受损或被杀死的间接作用都与HIV感染的免疫发病机制有关，因为在缺乏共刺激的情况下，主要组织相容性复合体（MHC）分子的T细胞受体结合通过CD 28与CD 80（B7-1）或CD 86（B7-2）的结合介导，我们确定了HIV-1病毒粒子是否整合了MHC-I类（MHC-I）、MHC-II、CD 80或CD 86。还评价了由匹配的未感染细胞产生的微泡。HIV感染增加了T和B细胞系、巨噬细胞和外周血单核细胞（PBMC）上MHC-II的表达，但没有显着改变CD 80或CD 86的表达。来自所有MHC-II阳性细胞类型的HIV病毒体掺入高水平的MHC-II，并且与CD 80相比，病毒体和微泡都优先掺入CD 86。在细胞上以高水平表达的CD 45被鉴定为在微泡上以高水平存在的蛋白质，但在HIV-1病毒体上未检测到。病毒体相关的宿主细胞衍生分子影响非感染性HIV病毒体在新鲜分离的PBMC中触发死亡的能力。这些结果表明，出芽的HIV-1病毒体优先掺入或排除宿主细胞蛋白，并表明HIV-1病毒体上存在的宿主细胞蛋白可能有助于HIV-1感染的总体发病机制。
Human immunodeficiency virus (HIV) infection results in a functional impairment of CD4(+) T cells long before a quantitative decline in circulating CD4(+) T cells is evident. The mechanism(s) responsible for this functional unresponsiveness and eventual depletion of CD4(+) T cells remains unclear. Both direct effects of cytopathic infection of CD4' cells and indirect effects in which uninfected "bystander" cells are functionally compromised or killed have been implicated as contributing to the immunopathogenesis of HIV infection, Because T-cell receptor engagement of major histocompatibility complex (MHC) molecules in the absence of costimulation mediated via CD28 binding to CD80 (B7-1) or CD86 (B7-2) can Lead to anergy or apoptosis, we determined whether HIV type 1 (HIV-1) virions incorporated MHC class I (MHC-I), MHC-II, CD80, or CD86. Microvesicles produced from matched uninfected cells were also evaluated. HIV infection increased MHC-II expression on T- and B-cell lines, macrophages, and peripheral blood mononclear cells (PBMC) but did not significantly alter the expression of CD80 or CD86. HIV virions derived from all MHC-II-positive cell types incorporated high levels of MHC-II, and both virions and microvesicles preferentially incorporated CD86 compared to CD80. CD45, expressed at high levels on cells, was identified as a protein present at high levels on microvesicles but was not detected on HIV-1 virions. Virion-associated, host cell-derived molecules impacted the ability of noninfectious HIV virions to trigger death in freshly isolated PBMC, These results demonstrate the preferential incorporation or exclusion of host cell proteins by budding HIV-1 virions and suggest that host cell proteins present on HIV-1 virions may contribute to the overall pathogenesis of HIV-I infection.