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

Virology. 2001 May 10;283(2):230-9. doi: 10.1006/viro.2001.0856.

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/ISGF3 gamma/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cysteine Endopeptidases / metabolism
  • DNA, Complementary
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Interferon Type I / immunology*
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / metabolism
  • Parainfluenza Virus 2, Human / genetics
  • Parainfluenza Virus 2, Human / metabolism
  • Parainfluenza Virus 2, Human / pathogenicity*
  • Proteasome Endopeptidase Complex
  • Protein Processing, Post-Translational
  • RNA, Messenger / metabolism
  • Rubulavirus Infections / physiopathology
  • Rubulavirus Infections / virology
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Transfection
  • Viral Proteins*
  • Viral Structural Proteins / genetics
  • Viral Structural Proteins / metabolism*

Substances

  • DNA, Complementary
  • DNA-Binding Proteins
  • IRF9 protein, human
  • Interferon Type I
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Multienzyme Complexes
  • RNA, Messenger
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • Trans-Activators
  • Transcription Factors
  • V protein, human parainfluenza virus type 1
  • Viral Proteins
  • Viral Structural Proteins
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex