Apr 10, 2020

MARCH8 inhibits viral infection by two different mechanisms

BioRxiv : the Preprint Server for Biology
Y. ZhangKenzo Tokunaga


Membrane-associated RING-CH (MARCH) family members are cellular transmembrane proteins that downregulate several host membrane proteins. We have recently reported that one family member, MARCH8, inhibits infection with both HIV-1 and vesicular stomatitis virus G-glycoprotein (VSV-G)-pseudotyped viruses by reducing virion incorporation of envelope glycoproteins. The molecular mechanisms by which MARCH8 targets envelope glycoproteins remain unknown. Here, we show two different mechanisms by which MARCH8 inhibits viral infection. Viruses pseudotyped with the VSV-G mutant, in which cytoplasmic lysine residues were mutated, were insensitive to the inhibitory effect of MARCH8, whereas those with a similar lysine mutant of HIV-1 Env remained sensitive to it. Ubiquitination assays showed that wild-type VSV-G, but not its lysine mutant, was ubiquitinated by MARCH8. Furthermore, the MARCH8 mutant, which had a disrupted cytoplasmic tyrosine motif that is critical for intracellular protein sorting, did not inhibit HIV-1 Env-mediated infection, while it still impaired infection by VSV-G-pseudotyped viruses. Overall, we conclude that MARCH8 impairs viral infectivity by downregulating envelope glycoproteins through two different mechanisms me...Continue Reading

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Mentioned in this Paper

Molecular Probe Techniques
Cell Death

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