title: TRIM79α, an interferon-stimulated gene product, restricts tick-borne encephalitis virus replication by degrading the viral RNA polymerase.
abstract: In response to virus infection, type I interferons (IFNs) induce several genes, most of whose functions are largely unknown. Here, we show that the tripartite motif (TRIM) protein, TRIM79α, is an IFN-stimulated gene (ISG) product that specifically targets tick-borne encephalitis virus (TBEV), a Flavivirus that causes encephalitides in humans. TRIM79α restricts TBEV replication by mediating lysosome-dependent degradation of the flavivirus NS5 protein, an RNA-dependent RNA polymerase essential for virus replication. NS5 degradation was specific to tick-borne flaviviruses, as TRIM79α did not recognize NS5 from West Nile virus (WNV) or inhibit WNV replication. In the absence of TRIM79α, IFN-β was less effective in inhibiting tick-borne flavivirus infection of mouse macrophages, highlighting the importance of a single virus-specific ISG in establishing an antiviral state. The specificity of TRIM79α for TBEV reveals a remarkable ability of the innate IFN response to discriminate between closely related flaviviruses.
authors.affiliation: Innate Immunity and Pathogenesis Unit, Laboratory of Virology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: R Travis
authors.initials: RT
authors.lastname: Taylor
authors.forename: Kirk J
authors.initials: KJ
authors.lastname: Lubick
authors.forename: Shelly J
authors.initials: SJ
authors.lastname: Robertson
authors.forename: James P
authors.initials: JP
authors.lastname: Broughton
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Bloom
authors.forename: Wade A
authors.initials: WA
authors.lastname: Bresnahan
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Best
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism*; D004669:Encephalitis Viruses, Tick-Borne / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D004675:Encephalitis, Tick-Borne / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; C569484:TRIM79alpha protein, mouse; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases