Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

E Miyagi, AJ Andrew, S Kao… - Proceedings of the …, 2009 - National Acad Sciences
E Miyagi, AJ Andrew, S Kao, K Strebel
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
HIV-1 Vpu enhances the release of virions from infected cells. Recent work identified Bst-
2/CD317/tetherin as a host factor whose inhibitory activity on viral release is counteracted by
Vpu. A current working model proposes that Bst-2 inhibits virus release by tethering viral
particles to the cell surface. Here, we analyzed endogenous Bst-2 with respect to its effect on
virus release from HeLa cells, T cells, and macrophages. We noted significant cell type-
dependent variation in Bst-2 expression. Vpu caused a reduction in Bst-2 expression in …
HIV-1 Vpu enhances the release of virions from infected cells. Recent work identified Bst-2/CD317/tetherin as a host factor whose inhibitory activity on viral release is counteracted by Vpu. A current working model proposes that Bst-2 inhibits virus release by tethering viral particles to the cell surface. Here, we analyzed endogenous Bst-2 with respect to its effect on virus release from HeLa cells, T cells, and macrophages. We noted significant cell type-dependent variation in Bst-2 expression. Vpu caused a reduction in Bst-2 expression in transfected HeLa cells and long-term infected macrophages. However, Vpu expression did not result in cell surface down-modulation of Bst-2 or a reduction in intracellular Bst-2 expression in CEMx174 or H9 cells, yet virus replication in these cells was Vpu-responsive. Surprisingly, Bst-2 was undetectable in cell-free virions that were recovered from the surface of HeLa cells by physical shearing, suggesting that a tethering model may not explain all of the functional properties of Bst-2. Taken together we conclude that enhancement of virus release by Vpu does not, at least in CEMx174 and H9 cells, require cell surface down-modulation or intracellular depletion of Bst-2, nor does it entail exclusion of Bst-2 from viral particles.
National Acad Sciences