Identification of Interferon-Stimulated Genes with Antiretroviral Activity

Melissa Kane, Trinity M. Zang, Suzannah J. Rihn, Fengwen Zhang, Tonya Kueck, Mudathir Alim, John Schoggins, Charles M. Rice, Sam J. Wilson, Paul D. Bieniasz

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)392-405
Number of pages14
JournalCell Host and Microbe
Volume20
Issue number3
DOIs
StatePublished - Sep 14 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Kane, M., Zang, T. M., Rihn, S. J., Zhang, F., Kueck, T., Alim, M., Schoggins, J., Rice, C. M., Wilson, S. J., & Bieniasz, P. D. (2016). Identification of Interferon-Stimulated Genes with Antiretroviral Activity. Cell Host and Microbe, 20(3), 392-405. https://doi.org/10.1016/j.chom.2016.08.005