Identification of five interferon-induced cellular proteins that inhibit West Nile virus and dengue virus infections

Dong Jiang, Jessica M. Weidner, Min Qing, Xiao Ben Pan, Haitao Guo, Chunxiao Xu, Xianchao Zhang, Alex Birk, Jinhong Chang, Pei Yong Shi, Timothy M. Block, Ju Tao Guo

Research output: Contribution to journalArticle

217 Scopus citations

Abstract

Interferons (IFNs) are key mediators of the host innate antiviral immune response. To identify IFN-stimulated genes (ISGs) that instigate an antiviral state against two medically important flaviviruses, West Nile virus (WNV) and dengue virus (DENV), we tested 36 ISGs that are commonly induced by IFN-α for antiviral activity against the two viruses. We discovered that five ISGs efficiently suppressed WNV and/or DENV infection when they were individually expressed in HEK293 cells. Mechanistic analyses revealed that two structurally related cell plasma membrane proteins, IFITM2 and IFITM3, disrupted early steps (entry and/or uncoating) of the viral infection. In contrast, three IFN-induced cellular enzymes, viperin, ISG20, and double-stranded-RNA-activated protein kinase, inhibited steps in viral proteins and/or RNA biosynthesis. Our results thus imply that the antiviral activity of IFN-α is collectively mediated by a panel of ISGs that disrupt multiple steps of the DENV and WNV life cycles.

Original languageEnglish (US)
Pages (from-to)8332-8341
Number of pages10
JournalJournal of virology
Volume84
Issue number16
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Jiang, D., Weidner, J. M., Qing, M., Pan, X. B., Guo, H., Xu, C., Zhang, X., Birk, A., Chang, J., Shi, P. Y., Block, T. M., & Guo, J. T. (2010). Identification of five interferon-induced cellular proteins that inhibit West Nile virus and dengue virus infections. Journal of virology, 84(16), 8332-8341. https://doi.org/10.1128/JVI.02199-09