title: Vpu-mediated tetherin antagonism of ongoing HIV-1 infection in CD4(+) T-cells is not directly related to the extent of tetherin cell surface downmodulation.
abstract: Tetherin is a host cell restriction factor that acts against HIV-1 and other enveloped viruses. The antiviral activity of tetherin is antagonized by the HIV-1 protein Vpu, that downregulates tetherin from the cell surface. Here, we report the specific detection of cell surface tetherin levels in primary activated CD4(+) T-cells and in CD4(+) T-cell lines. Differences were observed regarding tetherin cell surface expression, Vpu-mediated tetherin downmodulation and promotion of virus release. However, Vpu expression in all T-cell lines resulted in a 2-fold increase in numbers of infected cells after three days. This implies a Vpu-mediated effect in ongoing infection and possibly in cell-to-cell viral spread that is independent of the extent of Vpu-mediated tetherin cell surface downmodulation. Endogenous cell surface tetherin levels in T-cell lines were also downmodulated following infection with Vpu-deleted virus, suggesting an additional Vpu-independent mechanism of tetherin cell surface downmodulation following HIV-1 infection in T-cell lines.
authors.affiliation: McGill University AIDS Center, Lady Davis Institute, Jewish General Hospital, Montréal, Canada. bjorn.kuhl@mail.mcgill.ca
authors.forename: Björn D
authors.initials: BD
authors.lastname: Kuhl
authors.forename: Richard D
authors.initials: RD
authors.lastname: Sloan
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Donahue
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D015703:Antigens, CD; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology; D054884:Host-Pathogen Interactions; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; 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