Identification of interferon-stimulated genes with antiretroviral activity

Kane, M., Zang, T. M., Rihn, S. J. , Zhang, F., Kueck, T., Alim, M., Schoggins, J., Rice, C. M., Wilson, S. J. and Bieniasz, P. D. (2016) Identification of interferon-stimulated genes with antiretroviral activity. Cell Host and Microbe, 20(3), pp. 392-405. (doi: 10.1016/j.chom.2016.08.005) (PMID:27631702) (PMCID:PMC5026698)

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Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.

Item Type:Articles
Additional Information:This work was supported by grants from the NIH R3764003 (to P.D.B.), 1F32AI116263-01 (to M.K.), AI091707 (to J.S. and C.M.R.), and UK MRC MR/K024752/1 (to S.J.W.).
Glasgow Author(s) Enlighten ID:Rihn, Dr Suzannah and Wilson, Dr Sam
Authors: Kane, M., Zang, T. M., Rihn, S. J., Zhang, F., Kueck, T., Alim, M., Schoggins, J., Rice, C. M., Wilson, S. J., and Bieniasz, P. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cell Host and Microbe
Publisher:Elsevier (Cell Press)
ISSN (Online):1934-6069
Published Online:14 September 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Cell Host and Microbe 20(3): 392-405
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