TRIM79α, an interferon-stimulated gene product, restricts tick-borne encephalitis virus replication by degrading the viral RNA polymerase

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 Flav...

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Published inCell host & microbe Vol. 10; no. 3; pp. 185 - 196
Main Authors Taylor, R Travis, Lubick, Kirk J, Robertson, Shelly J, Broughton, James P, Bloom, Marshall E, Bresnahan, Wade A, Best, Sonja M
Format Journal Article
LanguageEnglish
Published United States 15.09.2011
Subjects
Animals
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Line
DNA-Directed RNA Polymerases - genetics
DNA-Directed RNA Polymerases - metabolism
Encephalitis Viruses, Tick-Borne - enzymology
Encephalitis Viruses, Tick-Borne - genetics
Encephalitis Viruses, Tick-Borne - physiology
Encephalitis, Tick-Borne - genetics
Encephalitis, Tick-Borne - metabolism
Encephalitis, Tick-Borne - virology
Humans
Mice
Mice, Inbred C57BL
Protein Binding
Viral Proteins - genetics
Viral Proteins - metabolism
Virus Replication
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Summary: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.
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ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2011.08.004