Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon-beta production by interfering with the RIG-I signaling pathway.
Porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of an economically important swine disease that has been devastating the swine industry since the late 1980s. Accumulating evidences have revealed that PRRSV infection fails to induce type I interferon (IFN-alpha/beta), which are normally induced rapidly during virus replication in virus-infected cells. However, the potential mechanisms remain largely unclear. In this study, we showed that PRRSV infection activated the signal transduction components of NF-kappaB and AP-1, but not of interferon regulatory factor 3 (IRF3), an essential IFN-beta transcription factor. Furthermore, PRRSV infection significantly blocked synthetic dsRNA-induced IFN-beta production and IRF3 nuclear translocation. To better understand the upstream signaling events that suppress IRF3 activation, we further investigated the roles of individual components of the retinoic acid-inducible gene I (RIG-I)- and Toll-like receptor 3 (TLR3)-mediated signaling pathway for IFN-beta production during PRRSV infection. We observed that PRRSV infection significantly inhibited dsRNA-induced IRF3 activation and IFN-beta generation by inactivating IFN-beta promoter stimulator 1 (IPS-1), an adaptor molecule of RIG-I. In contrast, PRRSV infection only partially reduced the activation of TIR domain-containing adaptor inducing IFN-beta (TRIF), an adaptor molecule of TLR3. Our results suggest that PRRSV infection suppresses production of IFN-beta primarily by interfering with the IPS-1 activation in the RIG-I signaling pathway.
Luo
Rui
R
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
Xiao
Shaobo
S
Jiang
Yunbo
Y
Jin
Hui
H
Wang
Dang
D
Liu
Manli
M
Chen
Huanchun
H
Fang
Liurong
L
D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000187:drug effects / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D012330:RNA, Double-Stranded / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine / Q000276:immunology* / Q000821:virology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D018808:Transcription Factor AP-1; D016899:Interferon-beta; D051550:I-kappa B Kinase; D053487:DEAD-box RNA Helicases; D011070:Poly I-C