Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

• Published in: Scientific reports Vol. 6; no. 1; p. 20425
• Main Authors: Li, Sam X, Barrett, Bradley S, Guo, Kejun, Kassiotis, George, Hasenkrug, Kim J, Dittmer, Ulf, Gibbert, Kathrin, Santiago, Mario L
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 05.02.2016
• Subjects: Acute Disease; Animals; Antigen presentation; Antigens, CD - genetics; Antigens, CD - metabolism; B7-1 Antigen - metabolism; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD80 antigen; Cell activation; Cells, Cultured; Cytidine Deaminase - deficiency; Cytidine Deaminase - genetics; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Friend murine leukemia virus - genetics; Friend murine leukemia virus - physiology; Immunomodulation; Infections; Interleukin-15 - metabolism; Interleukin-2 - analysis; Interleukin-2 - metabolism; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Lymphocyte Activation; Lymphocytes T; Major histocompatibility complex; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Natural killer cells; NF-kappa B - metabolism; NIH 3T3 Cells; Phenotype; Replication; Retroviridae Infections - metabolism; Retroviridae Infections - pathology; Retroviridae Infections - veterinary; RNA, Viral - blood; Rodents; T cell receptors; Virions; Virus Replication
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20425

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.