title: Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection.
abstract: Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation.
authors: Department of Medicine, Aurora, University of Colorado Denver, CO 80045, USA.|Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO 80045, USA.
authors: Sam X
authors: SX
authors: Li
authors: Department of Medicine, Aurora, University of Colorado Denver, CO 80045, USA.
authors: Bradley S
authors: BS
authors: Barrett
authors: Department of Medicine, Aurora, University of Colorado Denver, CO 80045, USA.
authors: Kejun
authors: K
authors: Guo
authors: The Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors: George
authors: G
authors: Kassiotis
authors: Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors: Kim J
authors: KJ
authors: Hasenkrug
authors: Institute for Virology, University Hospital in Essen, University of Duisburg-Essen, Essen, Germany.
authors: Ulf
authors: U
authors: Dittmer
authors: Institute for Virology, University Hospital in Essen, University of Duisburg-Essen, Essen, Germany.
authors: Kathrin
authors: K
authors: Gibbert
authors: Department of Medicine, Aurora, University of Colorado Denver, CO 80045, USA.|Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO 80045, USA.
authors: Mario L
authors: ML
authors: Santiago
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005622:Friend murine leukemia virus / Q000235:genetics / Q000502:physiology*; D019409:Interleukin-15 / Q000378:metabolism; D007376:Interleukin-2 / Q000032:analysis / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D041681:NIH 3T3 Cells; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D012192:Retroviridae Infections / Q000378:metabolism / Q000473:pathology* / Q000662:veterinary; D014779:Virus Replication; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D003564:Cytidine Deaminase; D019409:Interleukin-15; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012367:RNA, Viral; C513868:BST2 protein, mouse; D000074010:Bone Marrow Stromal Antigen 2; C503504:Apobec3 protein, mouse