title: Bst2/Tetherin Is Induced in Neurons by Type I Interferon and Viral Infection but Is Dispensable for Protection against Neurotropic Viral Challenge.
abstract: In permissive mouse central nervous system (CNS) neurons, measles virus (MV) spreads in the absence of hallmark viral budding or neuronal death, with transmission occurring efficiently and exclusively via the synapse. MV infection also initiates a robust type I interferon (IFN) response, resulting in the synthesis of a large number of genes, including bone marrow stromal antigen 2 (Bst2)/tetherin/CD317. Bst2 restricts the release of some enveloped viruses, but to date, its role in viral infection of neurons has not been assessed. Consequently, we investigated how Bst2 was induced and what role it played in MV neuronal infection. The magnitude of induction of neuronal Bst2 RNA and protein following IFN exposure and viral infection was notably higher than in similarly treated mouse embryo fibroblasts (MEFs). Bst2 synthesis was both IFN and Stat1 dependent. Although Bst2 prevented MV release from nonneuronal cells, its deletion had no effect on viral pathogenesis in MV-challenged mice. Our findings underscore how cell-type-specific differences impact viral infection and pathogenesis.
  
  
  OBJECTIVE
  Viral infections of the central nervous system can lead to debilitating disease and death. Moreover, it is becoming increasingly clear that nonrenewable cells, including most central nervous system neurons, combat neurotropic viral infections in fundamentally different ways than other rapidly dividing and renewable cell populations. Here we identify type I interferon signaling as a key inducer of a known antiviral protein (Bst2) in neurons. Unexpectedly, the gene is dispensable for clearance of neurotropic viral infection despite its well-defined contribution to limiting the spread of enveloped viruses in proliferating cells. A deeper appreciation of the importance of cell type heterogeneity in antiviral immunity will aid in the identification of unique therapeutic targets for life-threatening viral infections.
authors: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA Program in Blood Cell Development and Function, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors: Alicia M
authors: AM
authors: Holmgren
authors: Program in Blood Cell Development and Function, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA Program in Cell and Molecular Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Katelyn D
authors: KD
authors: Miller
authors: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA Program in Blood Cell Development and Function, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors: Sarah E
authors: SE
authors: Cavanaugh
authors: Program in Blood Cell Development and Function, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA glenn.rall@fccc.edu.
authors: Glenn F
authors: GF
authors: Rall
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D007370:Interferon Type I / Q000378:metabolism*; D008457:Measles / Q000276:immunology*; D008459:Measles virus / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D017931:DNA Primers; D007370:Interferon Type I; D008562:Membrane Glycoproteins; C513868:BST2 protein, mouse; D000074010:Bone Marrow Stromal Antigen 2