title: The cysteine protease domain of porcine reproductive and respiratory syndrome virus non-structural protein 2 antagonizes interferon regulatory factor 3 activation.
abstract: 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.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zheng
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Zhengli
authors.initials: Z
authors.lastname: Shi
authors.forename: Qinxue
authors.initials: Q
authors.lastname: Hu
authors.forename: Hanzhong
authors.initials: H
authors.lastname: Wang
mesh_terms: 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
chemical_list: D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta; D003546:Cysteine Endopeptidases; C078306:nsP2 proteinase