title: Identification of an antiviral host transmembrane protein MARCH8.
abstract: Membrane-associated RING-CH 8 (MARCH8) is one of 11 members of the recently discovered MARCH family of RING-finger E3 ubiquitin ligases. MARCH8 downregulates several host transmembrane proteins; however, its physiological roles remain unknown. Here we identify MARCH8 as a novel antiviral factor. The overexpression of MARCH8 in virus producing cells did not affect levels of lentivirus production, but markedly reduced viral infectivity. MARCH8 blocked the incorporation of HIV-1 envelope glycoprotein into virions by downregulating it from the cell surface, probably through their interaction, resulting in reduced viral entry efficiency. The inhibitory effect of MARCH8 on vesicular stomatitis virus G-glycoprotein was even more remarkable, suggesting a broad-spectrum inhibition of enveloped viruses by MARCH8. Importantly, the endogenous expression of MARCH8 was high in monocyte-derived macrophages and dendritic cells, and MARCH8 depletion in macrophages significantly increased the infectivity of virions produced from these cells. Our findings thus indicate that MARCH8, which is highly expressed in terminally differentiated myeloid cells, is a potent antiviral host transmembrane protein that reduces virion incorporation of viral envelope glycoproteins.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: D000998:Antiviral Agents; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D006023:Glycoproteins / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D016086:Lentivirus / Q000472:pathogenicity*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008562:Membrane Glycoproteins / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism / Q000821:virology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000378:metabolism; D014771:Virion / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; C028391:G protein, vesicular stomatitis virus; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C568898:MARCHF8 protein, human; D044767:Ubiquitin-Protein Ligases