The V protein of human parainfluenza virus 2 antagonizes type 1 interferonresponses by destabilizing signal transducer and activator of transcription 2

Type I interferon (IFN) induces antiviral responses through the activation of the ISGF3 transcription factor complex that contains the subunit protein s STAT1, STAT2, and p48/ISGF3 gamma /IRF9. The ability of some human paramy xoviruses 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 fram e blocks IFN-dependent transcriptional responses in the absence of other vi ral proteins. The loss of IFN response is due to V-protein-induced proteoly tic 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 effect s on STAT2 mRNA levels were observed. The results indicate that the V prote in of HPIV2 is sufficient to recognize and target a specific cellular trans cription factor for destruction by cellular machinery. (C) 2001 Academic Pr ess.