title: Upregulation of BST-2/Tetherin by HIV infection in vivo.
abstract: The interferon-inducible antiviral factor BST-2 prevents several enveloped viruses, including HIV, from escaping infected cells. The HIV protein Vpu antagonizes this host defense. Little is known about the expression of BST-2 during HIV infection in vivo and whether it can be modulated to the host's advantage. We studied the expression of BST-2 on blood cells from HIV-infected patients during the acute and chronic phases of disease as well as after antiretroviral treatment (ART). The expression of BST-2 was increased on mononuclear leukocytes, including CD4-positive T lymphocytes from HIV-positive patients, compared to that on cells of uninfected controls. The expression of BST-2 was highest during acute infection and decreased to levels similar to those of uninfected individuals after ART. Treatment of primary blood mononuclear cells in vitro with alpha interferon or with Toll-like receptor (TLR) agonists increased the expression of BST-2 to levels similar to those found during infection in vivo. The interferon-induced levels were sufficient to overcome the Vpu protein in vitro, reducing the release of wild-type HIV. These data show that BST-2 is upregulated during HIV infection, consistent with its role as an interferon-stimulated gene. The data further suggest that this upregulation is sufficient to saturate the activity of Vpu and inhibit wild-type HIV.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093-0679, USA. shshomann@googlemail.com
authors.forename: Stefanie
authors.initials: S
authors.lastname: Homann
authors.forename: Davey
authors.initials: D
authors.lastname: Smith
authors.forename: Susan
authors.initials: S
authors.lastname: Little
authors.forename: Douglas
authors.initials: D
authors.lastname: Richman
authors.forename: John
authors.initials: J
authors.lastname: Guatelli
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage; D015703:Antigens, CD / Q000096:biosynthesis*; D023241:Antiretroviral Therapy, Highly Active; D002478:Cells, Cultured; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D015854:Up-Regulation; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D058851:GPI-Linked Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2