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感染HIV-2的巨噬细胞产生并积累传染性较差的病毒颗粒。

HIV-2-Infected Macrophages Produce and Accumulate Poorly Infectious Viral Particles.

作者信息

Gea-Mallorquí Ester, Zablocki-Thomas Laurent, Maurin Mathieu, Jouve Mabel, Rodrigues Vasco, Ruffin Nicolas, Benaroch Philippe

机构信息

Institut Curie, PSL∗ Research University, INSERM U932, Paris, France.

Institut Curie, PSL∗ Research University, UMR3216, Paris, France.

出版信息

Front Microbiol. 2020 Jul 10;11:1603. doi: 10.3389/fmicb.2020.01603. eCollection 2020.

Abstract

A significant proportion of HIV-2-infected patients exhibit natural virological control that is generally absent from HIV-1-infected patients. Along with CD4 T cells, HIV-1 targets macrophages which may contribute to viral spreading and the latent reservoir. We have studied the relationship between macrophages and HIV-2, focusing on post-entry steps. HIV-2-infected monocyte-derived macrophages (MDMs) produced substantial amounts of viral particles that were largely harbored intracellularly. New viruses assembled at the limiting membrane of internal compartments similar to virus-containing compartments (VCCs) described for HIV-1. VCCs from MDMs infected with either virus shared protein composition and morphology. Strikingly, HIV-2 Gag was mostly absent from the cytosol and almost exclusively localized to the VCCs, whereas HIV-1 Gag was distributed in both locations. Ultrastructural analyses of HIV-2-infected MDMs revealed the presence of numerous VCCs containing both immature and mature particles in the lumen. HIV-2 particles produced by MDMs were poorly infectious in reporter cells and in transmission to activated T cells through a process that appeared independent of BST2 restriction. Rather than being involved in viral spreading, HIV-2-infected macrophages may represent a cell-associated source of viral antigens that can participate in the immune control of HIV-2 infection.

摘要

相当一部分感染HIV-2的患者表现出自然病毒学控制,而这在感染HIV-1的患者中通常不存在。除了CD4 T细胞,HIV-1还靶向巨噬细胞,这可能有助于病毒传播和潜伏库的形成。我们研究了巨噬细胞与HIV-2之间的关系,重点关注病毒进入后的步骤。感染HIV-2的单核细胞衍生巨噬细胞(MDM)产生了大量病毒颗粒,这些颗粒大多滞留在细胞内。新病毒在内质网的限制膜处组装,类似于描述的HIV-1含病毒区室(VCC)。感染任一病毒的MDM的VCC具有相同的蛋白质组成和形态。引人注目的是,HIV-2 Gag大多不存在于细胞质中,几乎只定位于VCC,而HIV-1 Gag则分布于这两个位置。对感染HIV-2的MDM的超微结构分析显示,管腔内存在大量含有未成熟和成熟颗粒的VCC。MDM产生的HIV-2颗粒在报告细胞中感染性较差,并且在通过一个似乎独立于BST2限制的过程传播至活化T细胞时也表现出较低的感染性。感染HIV-2的巨噬细胞可能并非参与病毒传播,而是代表一种与细胞相关的病毒抗原来源,可参与HIV-2感染的免疫控制。

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