甘露糖受体 1 限制感染巨噬细胞中 HIV 颗粒的释放。
Mannose Receptor 1 Restricts HIV Particle Release from Infected Macrophages.
机构信息
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Building 4, Room 312, 4 Center Drive, MSC 0460, Bethesda, MD 20892, USA.
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Building 4, Room 312, 4 Center Drive, MSC 0460, Bethesda, MD 20892, USA.
出版信息
Cell Rep. 2018 Jan 16;22(3):786-795. doi: 10.1016/j.celrep.2017.12.085.
Human mannose receptor 1 (hMRC1) is expressed on the surface of most tissue macrophages, dendritic cells, and select lymphatic or liver endothelial cells. HMRC1 contributes to the binding of HIV-1 to monocyte-derived macrophages (MDMs) and is involved in the endocytic uptake of HIV-1 into these cells. Here, we identify hMRC1 as an antiviral factor that inhibits virus release through a bone marrow stromal antigen 2 (BST-2)-like mechanism. Virions produced in the presence of hMRC1 accumulated in clusters at the cell surface but were fully infectious. HIV-1 counteracted the effect by transcriptional silencing of hMRC1. The effect of hMRC1 was not virus isolate specific. Surprisingly, deletion of the Env protein, which is known to interact with hMRC1, did not relieve the hMRC1 antiviral activity, suggesting the involvement of additional cellular factor(s) in the process. Our data reveal an antiviral mechanism that is active in primary human macrophages and is counteracted by HIV-1 through downregulation of hMRC1.
人甘露糖受体 1（hMRC1）表达于大多数组织巨噬细胞、树突状细胞和某些淋巴或肝内皮细胞表面。HMRC1 有助于 HIV-1 与单核细胞来源的巨噬细胞（MDMs）结合，并参与 HIV-1 进入这些细胞的内吞摄取。在这里，我们发现 hMRC1 是一种抗病毒因子，通过类似于骨髓基质抗原 2（BST-2）的机制抑制病毒释放。在 hMRC1 存在的情况下产生的病毒粒子在细胞表面聚集在簇中，但仍具有完全感染性。HIV-1 通过 hMRC1 的转录沉默来对抗这种作用。hMRC1 的作用不受病毒分离株特异性的影响。令人惊讶的是，Env 蛋白的缺失（已知与 hMRC1 相互作用）并没有减轻 hMRC1 的抗病毒活性，这表明该过程涉及其他细胞因子。我们的数据揭示了一种在原代人巨噬细胞中起作用的抗病毒机制，该机制被 HIV-1 通过下调 hMRC1 来拮抗。
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