Mannose Receptor 1 Restricts HIV Particle Release from Infected Macrophages
Sayaka Sukegawa,
Eri Miyagi,
Fadila Bouamr,
Helena Farkašová,
Klaus Strebel
Affiliations
Sayaka Sukegawa
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
Eri Miyagi
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
Fadila Bouamr
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
Helena Farkašová
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
Klaus Strebel
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
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.
