title: Tetherin promotes the innate and adaptive cell-mediated immune response against retrovirus infection in vivo.
abstract: Tetherin/BST-2 is a host restriction factor that could directly inhibit retroviral particle release by tethering nascent virions to the plasma membrane. However, the immunological impact of Tetherin during retrovirus infection remains unknown. We now show that Tetherin influences antiretroviral cell-mediated immune responses. In contrast to the direct antiviral effects of Tetherin, which are dependent on cell surface expression, the immunomodulatory effects are linked to the endocytosis of the molecule. Mice encoding endocytosis-competent C57BL/6 Tetherin exhibited lower viremia and pathology at 7 d postinfection with Friend retrovirus (FV) compared with mice encoding endocytosis-defective NZW/LacJ Tetherin. Notably, antiretroviral protection correlated with stronger NK cell responses. In addition, Friend retrovirus infection levels were significantly lower in wild-type C57BL/6 mice than in Tetherin knockout mice at 2 wk postinfection, and antiretroviral protection correlated with stronger NK cell and virus-specific CD8+ T cell responses. The results demonstrate that Tetherin acts as a modulator of the cell-mediated immune response against retrovirus infection in vivo.
authors.affiliation: Department of Medicine, University of Colorado, Denver, Aurora, CO 80045; Department of Microbiology, University of Colorado, Denver, Aurora, CO 80045;
authors.forename: Sam X
authors.initials: SX
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Colorado, Denver, Aurora, CO 80045;
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Barrett
authors.affiliation: Department of Medicine, University of Colorado, Denver, Aurora, CO 80045;
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Heilman
authors.affiliation: Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840;
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Messer
authors.affiliation: Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016;
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Liberatore
authors.affiliation: Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016;
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
authors.affiliation: Division of Immunoregulation, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom; and.
authors.forename: George
authors.initials: G
authors.lastname: Kassiotis
authors.affiliation: Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840;
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Hasenkrug
authors.affiliation: Department of Medicine, University of Colorado, Denver, Aurora, CO 80045; Department of Microbiology, University of Colorado, Denver, Aurora, CO 80045; Department of Immunology, University of Colorado, Denver, Aurora, CO 80045 mario.santiago@ucdenver.edu.
authors.forename: Mario L
authors.initials: ML
authors.lastname: Santiago
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005622:Friend murine leukemia virus / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014766:Viremia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D008562:Membrane Glycoproteins; C513868:BST2 protein, mouse; D000074010:Bone Marrow Stromal Antigen 2