The Human STAT2 Coiled-Coil Domain Contains a Degron for Zika Virus Interferon Evasion

Jean Patrick Parisien, Jessica J. Lenoir, Gloria Alvarado, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The ability of viruses to evade the host antiviral immune system determines their level of replication fitness, species specificity, and pathogenic potential. Flaviviruses rely on the subversion of innate immune barriers, including the type I and type III interferon (IFN) antiviral systems. Zika virus infection induces the degradation of STAT2, an essential component of the IFN-stimulated gene transcription factor ISGF3. The mechanisms that lead to STAT2 degradation by Zika virus are poorly understood, but it is known to be mediated by the viral NS5 protein that binds to STAT2 and targets it for proteasome-mediated destruction. To better understand how NS5 engages and degrades STAT2, functional analysis of the protein interactions that lead to Zika virus and NS5-dependent STAT2 proteolysis were investigated. Data implicate the STAT2 coiled-coil domain as necessary and sufficient for NS5 interaction and proteasome degradation after Zika virus infection. Molecular dissection reveals that the first two a-helices of the STAT2 coiled-coil domain contain a specific targeting region for IFN antagonism. These functional interactions provide a more complete understanding of the essential protein-protein interactions needed for Zika virus evasion of the host antiviral response and identify new targets for antiviral therapeutic approaches.

Original languageEnglish (US)
Article numbere01301-21
JournalJournal of virology
Volume96
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • NS5
  • STAT2
  • Zika virus

ASJC Scopus subject areas

  • Insect Science
  • Virology
  • Microbiology
  • Immunology

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