Foot-and-mouth disease virus leader proteinase inhibits dsRNA-induced type I interferon transcription by decreasing interferon regulatory factor 3/7 in protein levels.
The leader proteinase (L(pro)) of foot-and-mouth disease virus (FMDV) has been identified as an interferon-beta (IFN-beta) antagonist that disrupts the integrity of transcription factor nuclear factor kappaB (NF-kappaB). In this study, we showed that the reduction of double stranded RNA (dsRNA)-induced IFN-alpha1/beta expression caused by L(pro) was also associated with a decrease of interferon regulatory factor 3/7 (IRF-3/7) in protein levels, two critical transcription factors for activation of IFN-alpha/beta. Furthermore, overexpression of L(pro) significantly reduced the transcription of multiple IRF-responsive genes including 2',5'-OAS, ISG54, IP-10, and RANTES. Screening L(pro) mutants indicated that the ability to process eIF-4G of L(pro) is not required for suppressing dsRNA-induced activation of the IFN-alpha1/beta promoter and decreasing IRF-3/7 expression. Taken together, our results demonstrate that, in addition to disrupting NF-kappaB, L(pro) also decreases IRF-3/7 expression to suppress dsRNA-induced type I IFN production, suggesting multiple strategies used by FMDV to counteract the immune response to viral infection.
Wang
Dang
D
Huazhong Agricultural University, Wuhan, PR China.
Fang
Liurong
L
Luo
Rui
R
Ye
Rui
R
Fang
Ying
Y
Xie
Lilan
L
Chen
Huanchun
H
Xiao
Shaobo
S
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005536:Foot-and-Mouth Disease / Q000235:genetics / Q000276:immunology*; D029544:Foot-and-Mouth Disease Virus / Q000201:enzymology / Q000276:immunology*; D005786:Gene Expression Regulation; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000235:genetics; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012330:RNA, Double-Stranded / Q000276:immunology / Q000494:pharmacology; D014158:Transcription, Genetic
D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D012330:RNA, Double-Stranded; D010450:Endopeptidases; C088747:leader proteinase, foot-and-mouth disease virus; D011070:Poly I-C