The V protein of human parainfluenza virus 2 antagonizes type I interferon responses by destabilizing signal transducer and activator of transcription 2

Jean Patrick Parisien, Joe F. Lau, Jason J. Rodriguez, Brian M. Sullivan, Anne Moscona, Griffith D. Parks, Robert A. Lamb, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

188 Scopus citations

Abstract

Type I interferon (IFN) induces antiviral responses through the activation of the ISGF3 transcription factor complex that contains the subunit proteins STAT1, STAT2, and p48/ISGF3γ/IRF9. The ability of some human paramyxoviruses to overcome IFN actions by specific proteolysis of STAT proteins has been examined. Infection of cells with type 2, but not type 1 or type 3 human parainfluenza virus (HPIV) leads to a loss of cellular STAT2 protein. Expression of a single HPIV2 protein derived from the V open reading frame blocks IFN-dependent transcriptional responses in the absence of other viral proteins. The loss of IFN response is due to V-protein-induced proteolytic degradation of STAT2. Expression of HPIV2 V causes the normally stable STAT2 protein to be rapidly degraded, and this proteolytic activity can be partially alleviated by proteasome inhibition. No V-protein-specific effects on STAT2 mRNA levels were observed. The results indicate that the V protein of HPIV2 is sufficient to recognize and target a specific cellular transcription factor for destruction by cellular machinery

Original languageEnglish (US)
Pages (from-to)230-239
Number of pages10
JournalVirology
Volume283
Issue number2
DOIs
StatePublished - May 10 2001

Keywords

  • HPIV2
  • ISGF3
  • Interferon
  • Paramyxovirus
  • Proteolysis
  • STAT
  • V protein

ASJC Scopus subject areas

  • Virology

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