Reactivation from latency displays HIV particle budding at plasma membrane, accompanying CD44 upregulation and recruitment
Reactivation from latency displays HIV particle budding at plasma membrane, accompanying CD44 upregulation and recruitment
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潜伏期的重新激活显示 HIV 颗粒在质膜上出芽，伴随着 CD44 上调和募集
作者：
Mari Suyama;Eriko Daikoku;T. Goto;K. Sano;Y. Morikawa
背景人类免疫缺陷病毒(HIV)在T淋巴细胞中从细胞表面萌发，而在巨噬细胞中则萌发到细胞内的内小体。另一方面，最近的研究表明，即使在单核细胞中，艾滋病毒也优先从细胞表面发芽。然而，大多数研究都是基于对急性感染细胞的观察，对HIV萌芽伴随潜伏期重新激活的情况知之甚少。结果我们观察到在肿瘤坏死因子-α刺激后，潜伏感染的T淋巴细胞和单核细胞系中艾滋病毒的萌发，并检测了可能与颗粒产生有关的宿主因素的上调。电子显微镜分析显示，潜伏感染的J1.1细胞(潜伏感染HIV-1的Jurkat细胞)和U1细胞(潜伏感染HIV-1的U937细胞)重新激活后，HIV颗粒主要在质膜上萌发，这种形态类似于急性感染的Jurkat和U937细胞中的颗粒萌发。当用qRT-PCR定量检测mRNA的表达水平时，我们发现重新激活的J1.1和U1细胞产生的颗粒伴随着CD44的上调。当尤尔卡特和U937细胞被艾滋病毒-1急性感染时，这种上调也被观察到，但在仅用肿瘤坏死因子-α刺激时没有观察到，这表明CD44CD44上调与艾滋病毒的产生有关，但与细胞刺激无关。当U1细胞重新激活和U937细胞急性感染HIV-1时，CD63和HRS等内吞途径的分子也上调。共聚焦显微镜显示，这些上调的宿主分子聚集在质膜上形成成熟颗粒的部位。结论我们的研究表明，HIV颗粒在潜伏期重新激活时在质膜上萌发，这种形态类似于急性感染时的颗粒萌发。我们的数据还表明，HIV的表达可能导致某些宿主细胞分子上调，这些宿主细胞分子被招募到颗粒组装位置，可能协调颗粒的产生。
BackgroundIt has been accepted that HIV buds from the cell surface in T lymphocytes, whereas in macrophages it buds into intracellular endosomes. Recent studies, on the other hand, suggest that HIV preferentially buds from the cell surface even in monocytic cells. However, most studies are based on observations in acutely infected cells and little is known about HIV budding concomitant with reactivation from latency. Such studies would provide a better understanding of a reservoir for HIV.ResultsWe observed HIV budding in latently infected T lymphocytic and monocytic cell lines following TNF-α stimulation and examined the upregulation of host factors that may be involved in particle production. Electron microscopy analysis revealed that reactivation of latently infected J1.1 cells (latently infected Jurkat cells with HIV-1) and U1 cells (latently infected U937 cells with HIV-1) displayed HIV particle budding predominantly at the plasma membrane, a morphology that is similar to particle budding in acutely infected Jurkat and U937 cells. When mRNA expression levels were quantified by qRT-PCR, we found that particle production from reactivated J1.1 and U1 cells was accompanied by CD44 upregulation. This upregulation was similarly observed when Jurkat and U937 cells were acutely infected with HIV-1 but not when just stimulated with TNF-α, suggesting that CD44 upregulation was linked with HIV production but not with cell stimulation. The molecules in endocytic pathways such as CD63 and HRS were also upregulated when U1 cells were reactivated and U937 cells were acutely infected with HIV-1. Confocal microscopy revealed that these upregulated host molecules were recruited to and accumulated at the sites where mature particles were formed at the plasma membrane.ConclusionOur study indicates that HIV particles are budded at the plasma membrane upon reactivation from latency, a morphology that is similar to particle budding in acute infection. Our data also suggest that HIV expression may lead to the upregulation of certain host cell molecules that are recruited to sites of particle assembly, possibly coordinating particle production.
影响因子：
3.7
作者：
Geiss, GK;Bumgarner, RE;Katze, MG
通讯作者：
Katze, MG
HIV 诱导的单核细胞系 CD44 表达缺失。
DOI：
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发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Guo,MM;Hildreth,JE
通讯作者：
Hildreth,JE