Characterization of the early steps of infection of primary blood monocytes by human immunodeficiency virus type 1
Characterization of the early steps of infection of primary blood monocytes by human immunodeficiency virus type 1
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DOI：
10.1128/jvi.02321-07
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发表时间：
2008-07-01
影响因子：
5.4
通讯作者：
Cimarelli, Andrea
中科院分区：
文献类型：
--
作者：
Arfi, Vanessa;Riviere, Lise;Cimarelli, Andrea
血液循环单核细胞在组织中迁移以响应危险刺激，并在那里分化成免疫系统的两个主要参与者：巨噬细胞和树突状细胞。考虑到它们的迁移行为和它们在免疫应答的协调中的关键作用，单核细胞谱系的细胞是包括人类免疫缺陷病毒1型（HIV-1）在内的几种病毒的靶标并不奇怪。HIV-1在单核细胞样细胞中复制的程度受其分化状态的影响，并受外源性刺激的调节。未受刺激的单核细胞显示出对HIV感染的相对抗性，主要在病毒生命周期的早期阶段发挥作用。尽管进行了深入的研究，但受影响步骤的身份仍然存在争议，尽管通常认为它发生在病毒进入后。我们在这里重新审查的早期步骤病毒感染未受刺激的单核细胞使用水泡性口炎病毒G蛋白假型HIV-1病毒粒子。我们的数据表明，第一个块与这些颗粒的单核细胞感染的早期步骤发生在病毒进入的水平。进入后，逆转录和整合以极慢的动力学进行，而不是被阻断。一旦完成，病毒DNA分子延迟进入细胞核和整合长达5至6天。这些步骤的无效性解释了单核细胞在感染的早期阶段对HIV-1的抗性。
Blood-circulating monocytes migrate in tissues in response to danger stimuli and differentiate there into two major actors of the immune system: macrophages and dendritic cells. Given their migratory behavior and their pivotal role in the orchestration of immune responses, it is not surprising that cells of the monocyte lineage are the target of several viruses, including human immunodeficiency virus type 1 (HIV-1). HIV-1 replicates in monocytoid cells to an extent that is influenced by their differentiation status and modulated by exogenous stimulations. Unstimulated monocytes display a relative resistance to HIV infection mostly exerted during the early steps of the viral life cycle. Despite intensive studies, the identity of the affected step remains controversial, although it is generally assumed to take place after viral entry. We reexamine here the early steps of viral infection of unstimulated monocytes using vesicular stomatitis virus G protein-pseudotyped HIV-1 virions. Our data indicate that a first block to the early steps of infection of monocytes with these particles occurs at the level of viral entry. After entry, reverse transcription and integration proceed with extremely slow kinetics rather than being blocked. Once completed, viral DNA molecules delay entry into the nucleus and integration for up to 5 to 6 days. The inefficacy of these steps accounts for the resistance of monocytes to HIV-1 during the early steps of infection.