Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4361031 | Cell Host & Microbe | 2014 | 12 Pages |
•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
SummaryMost 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.
Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (406 K)Download as PowerPoint slide