The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation.
There is growing evidence that porcine reproductive and respiratory syndrome virus (PRRSV) has developed mechanisms to subvert the host innate immune response. PRRSV non-structural protein 2 (Nsp2) was suggested previously as a potential interferon (IFN) antagonist. This study focused on Nsp2 to investigate its inhibitory mechanism of IFN induction. It was demonstrated that Nsp2 strongly inhibited IFN-β production by antagonizing activation of the IFN regulatory factor 3 (IRF-3) pathway induced by the Sendai virus (SeV). Further studies revealed that the cysteine protease domain (PL2) of Nsp2 was necessary for IFN antagonism. Additionally, both full-length Nsp2 and the PL2 protease domain of Nsp2 were found to inhibit SeV-induced phosphorylation and nuclear translocation of IRF-3. These findings suggest that Nsp2 is likely to play an important role in subversion of IRF-3-dependent innate antiviral defences, providing a basis for elucidating the mechanisms underlying PRRSV pathogenesis.
Li
Hongxia
H
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
Zheng
Zhenhua
Z
Zhou
Peng
P
Zhang
Bing
B
Shi
Zhengli
Z
Hu
Qinxue
Q
Wang
Hanzhong
H
D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors*; D016899:Interferon-beta / Q000096:biosynthesis*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology* / Q000472:pathogenicity*; D017434:Protein Structure, Tertiary; D029082:Sendai virus / Q000276:immunology
D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta; D003546:Cysteine Endopeptidases; C078306:nsP2 proteinase