title: Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion.
abstract: 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.
authors.affiliation: Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA.
authors.forename: Eri
authors.initials: E
authors.lastname: Miyagi
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Andrew
authors.forename: Sandra
authors.initials: S
authors.lastname: Kao
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebel
mesh_terms: D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D015497:HIV-1 / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000502:physiology*; D006801:Humans; D007106:Immune Sera; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*; D014771:Virion; D019065:Virus Assembly; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D007106:Immune Sera; D008562:Membrane Glycoproteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins