Nef Proteins of Epidemic HIV-1 Group O Strains Antagonize Human Tetherin
Most simian immunodeficiency viruses use their Nef protein to antagonize the host restriction factor tetherin. A deletion in human tetherin confers Nef resistance, representing a hurdle to successful zoonotic transmission. HIV-1 group M evolved to utilize the viral protein U (Vpu) to counteract teth...
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Published in | Cell host & microbe Vol. 16; no. 5; pp. 639 - 650 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
12.11.2014
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Subjects | |
Online Access | Get full text |
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Summary: | Most simian immunodeficiency viruses use their Nef protein to antagonize the host restriction factor tetherin. A deletion in human tetherin confers Nef resistance, representing a hurdle to successful zoonotic transmission. HIV-1 group M evolved to utilize the viral protein U (Vpu) to counteract tetherin. Although HIV-1 group O has spread epidemically in humans, it has not evolved a Vpu-based tetherin antagonism. Here we show that HIV-1 group O Nef targets a region adjacent to this deletion to inhibit transport of human tetherin to the cell surface, enhances virion release, and increases viral resistance to inhibition by interferon-α. The Nef protein of the inferred common ancestor of group O viruses is also active against human tetherin. Thus, Nef-mediated antagonism of human tetherin evolved prior to the spread of HIV-1 group O and likely facilitated secondary virus transmission. Our results may explain the epidemic spread of HIV-1 group O.
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•HIV-1 group O Nef targets a distinct region adjacent to the deletion in human tetherin•Nef from the most recent common ancestor of HIV-1 group O counteracts human tetherin•HIV-1 O Nef proteins suppress anterograde transport of tetherin to the cell surface•Nef-mediated human tetherin downmodulation reduces IFNα sensitivity of HIV-1 group O
HIV-1 group O has infected about 100,000 individuals, but its mechanism of tetherin antagonism remained unknown. Kluge et al. find that group O Nef proteins evolved to counteract human tetherin by targeting a domain adjacent to a deletion that confers resistance against primate lentiviral Nef proteins, explaining the spread of HIV-1 group O. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Co-first author |
ISSN: | 1931-3128 1934-6069 1934-6069 |
DOI: | 10.1016/j.chom.2014.10.002 |