antagonism of tetherin restriction of hiv-1 release by vpu involves binding and sequestration of the restriction factor in a perinuclear compartment拮抗tetherin限制hiv - 1释放vpu包含绑定和封存的制约因素在细胞核周围的隔间.pdfVIP

Antagonism of Tetherin Restriction of HIV-1 Release by Vpu Involves Binding and Sequestration of the Restriction Factor in a Perinuclear Compartment ´ 1 1 1 1 1 Mathieu Dube , Bibhuti Bhusan Roy , Pierre Guiot-Guillain , Julie Binette , Johanne Mercier , Antoine 1 ´ 1,2 Chiasson , Eric A. Cohen * ´ 1 Laboratory of Human Retrovirology, Institut de recherches cliniques de Montreal (IRCM), Montreal, Quebec, Canada, 2 Department of Microbiology and Immunology, ´ ´ Universite de Montreal, Montreal, Quebec, Canada Abstract The Vpu accessory protein promotes HIV-1 release by counteracting Tetherin/BST-2, an interferon-regulated restriction factor, which retains virions at the cell-surface. Recent reports proposed b-TrCP-dependent proteasomal and/or endo-lysosomal degradation of Tetherin as potential mechanisms by which Vpu could down-regulate Tetherin cell-surface expression and antagonize this restriction. In all of these studies, Tetherin degradation did not, however, entirely account for Vpu anti-Tetherin activity. Here, we show that Vpu can promote HIV-1 release without detectably affecting Tetherin steady-state levels or turnover, suggesting that Tetherin degradation may not be necessary and/or sufficient for Vpu anti-Tetherin activity. Even though Vpu did not enhance Tetherin internalization from the plasma membrane (PM), it did significantly slow-down the overall transport of the protein towards the cell-surface. Accordingly, Vpu expression caused a specific removal of cell-surface Tetherin and a re-localization of the residual pool of Tetherin in a perinuclear co