The V protein of human parainfluenza virus 2 antagonizes type I interferon responses 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 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.
Parisien
J P
JP
Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Lau
J F
JF
Rodriguez
J J
JJ
Sullivan
B M
BM
Moscona
A
A
Parks
G D
GD
Lamb
R A
RA
Horvath
C M
CM
D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D010223:Parainfluenza Virus 2, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D019351:Rubulavirus Infections / Q000503:physiopathology / Q000821:virology; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014764:Viral Proteins; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C068854:V protein, human parainfluenza virus type 1; D014764:Viral Proteins; D015678:Viral Structural Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex