title: The amino acid at residue 155 in nonstructural protein 4 of porcine reproductive and respiratory syndrome virus contributes to its inhibitory effect for interferon-β transcription in vitro.
abstract: Type I interferons (IFNs), predominantly IFN-α and β, play important roles in both innate and adaptive immune responses against viral infections. Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized to be able to down-regulate the IFN response during in vivo and in vitro infection. In this study, we first analyzed inhibitory effect of each NSP of low pathogenic PRRSV HB-1/3.9 on IFN-β transcription in MARC-145 cells, and the results showed that the IFN-β promoter activation could be suppressed by NSP1α, NSP2, NSP1β, NSP3, NSP4, NSP5 and NSP11. We next confirmed that the inhibitory effect of NSP4 was mainly mediated through suppressing NF-κB activation, whereas not hindering NF-κB phosphorylation and nuclear translocation, and nuclear-localized NSP4 was responsible for inhibiting IFN-β activation. We further found that the NSP4 of different pathogenic PRRSV strains exhibited differential inhibitory effect on IFN-β, NF-κB, and IRF3 transcription, and the NSP4 of highly pathogenic (HP)-PRRSV could display more strong inhibitory effect. Finally, we determined that the amino acid at residue 155 in NSP4 contributed to its inhibitory effect for IFN-β transcription in vitro by altering its subcellular distribution. Our findings suggest that the nucleus-localized NSP4 of PRRSV participates in the modulation of the host type I IFNs system, and also provide novel insight for understanding the pathogenesis of the Chinese HP-PRRSV.
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, People's Republic of China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, People's Republic of China.
authors.forename: Mou
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, People's Republic of China.
authors.forename: Jige
authors.initials: J
authors.lastname: Du
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, People's Republic of China.
authors.forename: Xinna
authors.initials: X
authors.lastname: Ge
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address: guoxin@cau.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address: yanghanchun1@cau.edu.cn.
authors.forename: Hanchun
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D004252:DNA Mutational Analysis; D000882:Haplorhini; D054884:Host-Pathogen Interactions; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology*; D014158:Transcription, Genetic; D017361:Viral Nonstructural Proteins / Q000276:immunology*
chemical_list: D017361:Viral Nonstructural Proteins; D016899:Interferon-beta
keywords: In vitro; Inhibitory effect; Interferon-β (IFN-β); Nonstructural protein 4 (NSP4); Porcine reproductive and respiratory syndrome virus (PRRSV); Transcription