Bovine parainfluenza virus type 3 accessory proteins that suppress beta interferon production.
The paramyxovirus P gene encodes accessory proteins antagonistic to interferon (IFN). Viral proteins responsible for the IFN antagonism, however, are distinct among paramyxoviruses. Here we determine bovine parainfluenza virus type 3 (bPIV3) IFN antagonists that suppress IFN-beta production, and investigate the underlying molecular mechanism. Of bPIV3 P gene products, C and V proteins were found to suppress double-stranded RNA-stimulated IFN-beta production. The V protein of bPIV3 and Sendai virus in the same genus Respirovirus significantly inhibits double-stranded RNA-stimulated IFN-beta production and the IFN-beta promoter activation enhanced by overexpression of MDA5 but not RIG-I, and yet does not suppress IFN-beta production induced by TRIF, TBK1, and IKKi. The V protein of both viruses specifically binds to MDA5 but not RIG-I. These results suggest that the V protein targets MDA5 for blockage of the IFN-beta gene activation signal. On the other hand, both bPIV3 and Sendai virus C proteins modestly inhibited IFN-beta production irrespective of a species of the signaling molecules used as an inducer. Interestingly, reporter gene expression driven by various promoters was also suppressed by the C proteins irrespective of the promoter species. These results demonstrate that the target of the respirovirus C protein is undoubtedly different from that of the V protein.
Komatsu
Takayuki
T
Microbiology Section, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida-gun, Fukui 910-1193, Japan.
Takeuchi
Kenji
K
Gotoh
Bin
B
D000818:Animals; D002417:Cattle; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D029101:Parainfluenza Virus 3, Bovine / Q000472:pathogenicity*; D011971:Receptors, Immunologic; D015398:Signal Transduction; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D011971:Receptors, Immunologic; C111739:V protein, Sendai virus; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; D016899:Interferon-beta; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1