The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts.
Interferons initiate the host antiviral response by inducing a number of genes, most with no defined antiviral function. Here we show that the interferon-induced protein viperin inhibits influenza A virus release from the plasma membrane of infected cells. Viperin expression altered plasma membrane fluidity by affecting the formation of lipid rafts, which are detergent-resistant membrane microdomains known to be the sites of influenza virus budding. Intracellular interaction of viperin with farnesyl diphosphate synthase (FPPS), an enzyme essential for isoprenoid biosynthesis, decreased the activity of the enzyme. Overexpression of FPPS reversed viperin-mediated inhibition of virus production and restored normal membrane fluidity, and reduction of FPPS levels by siRNA inhibited virus release and replication, indicating that the FPPS interaction underlies viperin's effects. These findings suggest that targeting the release stage of the life cycle may affect the replication of many enveloped viruses. Furthermore, FPPS may be an attractive target for antiviral therapy.
Wang
Xiuyan
X
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8011, USA.
Hinson
Ella R
ER
Cresswell
Peter
P
D000998:Antiviral Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000502:physiology; D006367:HeLa Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006801:Humans; D007372:Interferons; D008560:Membrane Fluidity / Q000502:physiology; D021962:Membrane Microdomains / Q000502:physiology / Q000648:ultrastructure; D008854:Microscopy, Electron; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010957:Plasmids; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014779:Virus Replication; D000090123:Viperin Protein
D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007372:Interferons; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; C444427:RSAD2 protein, human; D000090123:Viperin Protein