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

Virology
J P ParisienCurt M Horvath

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.

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Citations

Sep 19, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Santanu Bose, Amiya K Banerjee
Jul 15, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Friedemann WeberPeter Staeheli
May 13, 2006·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Mounira K Chelbi-AlixDanielle Blondel
Aug 22, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Aparna Ramachandran, Curt M Horvath
Jan 27, 2005·Viral Immunology·Friedemann WeberOtto Haller
Apr 28, 2006·Antimicrobial Agents and Chemotherapy·M C Georges-CourbotV Deubel
Mar 13, 2009·Journal of Virology·Joseph AshourAdolfo García-Sastre
Jan 26, 2007·Journal of Virology·Joanne ElliottJames A Johnston
May 14, 2003·Journal of Virology·Christina M UlaneCurt M Horvath
Jun 28, 2003·Journal of Virology·Christopher F BaslerAdolfo García-Sastre

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