TRIM69 Inhibits Vesicular Stomatitis Indiana Virus.

Journal of Virology
Suzannah J. RihnSam J. Wilson

Abstract

Vesicular stomatitis Indiana virus (VSIV), formerly known as vesicular stomatitis virus (VSV) Indiana (VSVIND), is a model virus that is exceptionally sensitive to the inhibitory action of interferons (IFNs). Interferons induce an antiviral state by stimulating the expression of hundreds of interferon-stimulated genes (ISGs). These ISGs can constrain viral replication, limit tissue tropism, reduce pathogenicity, and inhibit viral transmission. Since VSIV is used as a backbone for multiple oncolytic and vaccine strategies, understanding how ISGs restrict VSIV not only helps in understanding VSIV-induced pathogenesis but also helps us evaluate and understand the safety and efficacy of VSIV-based therapies. Thus, there is a need to identify and characterize the ISGs that possess anti-VSIV activity. Using arrayed ISG expression screening, we identified TRIM69 as an ISG that potently inhibits VSIV. This inhibition was highly specific as multiple viruses, including influenza A virus, HIV-1, Rift Valley fever virus, and dengue virus, were unaffected by TRIM69. Indeed, just one amino acid substitution in VSIV can govern sensitivity/resistance to TRIM69. Furthermore, TRIM69 is highly divergent in human populations and exhibits signature...Continue Reading

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Citations

Oct 7, 2020·Acta Crystallographica. Section D, Structural Biology·Jeremy R KeownDavid C Goldstone
Dec 29, 2020·Frontiers in Immunology·Emily Yang, Melody M H Li
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Sep 29, 2021·Science·Arthur WickenhagenSam J Wilson

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Datasets Mentioned

BETA
AAC59275

Methods Mentioned

BETA
flow cytometry
PCR
FCS
transfection
Assay
transfections

Software Mentioned

Ensembl
ClustalW
MAFFT
TBLASTN
- Flu
Genewiz
PAML
CODEML
HyPhy
PhyML

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