TRIM69 inhibits vesicular stomatitis Indiana virus (VSIV)

Rihn, S. J. et al. (2019) TRIM69 inhibits vesicular stomatitis Indiana virus (VSIV). Journal of Virology, 93(20), e00951-19. (doi: 10.1128/JVI.00951-19) (PMID:31375575)

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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 signatures of positive selection that are consistent with this gene playing a key role in antiviral immunity. We propose that TRIM69 is an IFN-induced inhibitor of VSIV and speculate that TRIM69 could be important in limiting VSIV pathogenesis and might influence the specificity and/or efficacy of vesiculovirus-based therapies.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Palmarini, Professor Massimo and Sinkins, Professor Steven and Hughes, Dr Joseph and Herd, Dr Christie and Turnbull, Dr Matthew and Rihn, Dr Suzannah and Wilson, Professor Sam and Aziz, Muhamad Afiq Bin and Stewart, Mr Douglas and Sugrue, Dr Elena and Varela, Dr Mariana
Authors: Rihn, S. J., Aziz, M. A., Stewart, D. G., Hughes, J., Turnbull, M. L., Varela, M., Sugrue, E., Herd, C. S., Stanifer, M., Sinkins, S. P., Palmarini, M., and Wilson, S. J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN (Online):1098-5514
Published Online:02 August 2019
Copyright Holders:Copyright © 2019 Rihn et al.
First Published:First published in Journal of Virology 93(20):e00951-19
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
618831Identifying and characterising antiretroviral interferon stimulated genes (ISGs)Sam WilsonMedical Research Council (MRC)MR/K024752/1MVLS III - CENTRE FOR VIRUS RESEARCH
Innate Immunity and Host Species BarriersMassimo PalmariniMedical Research Council (MRC)MC_UU_12014/10III - Centre for Virus Research
3018400Host and Viral Determinants of Interferon Resistance During HIV-1 TransmissionSam WilsonMedical Research Council (MRC)MR/P022642/1III - Centre for Virus Research
Viral Genomics and BioinformaticsAndrew DavisonMedical Research Council (MRC)MC_UU_12014/12III-MRC-GU Centre for Virus Research
725951Inhibition of HIV-1 by Type II InterferonSuzannah RihnWellcome Trust (WELLCOTR)201366/Z/16/ZMVLS III - CENTRE FOR VIRUS RESEARCH