期刊
VIRUS RESEARCH
卷 189, 期 -, 页码 226-234出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.virusres.2014.05.027
关键词
Porcine reproductive and respiratory; syndrome virus (PRRSV); Nonstructural protein 4 (NSP4); Interferon-beta (IFN-beta); Transcription Inhibitory effect; In vitro
类别
资金
- National Key Basic Research Plan Grant from Chinese Ministry of Science and Technology [2014CB542700]
- Key project of National Natural Science Funds from National Natural Science Foundation of China [31330077]
- earmarked fund for Modern Agro-industry Technology Research System of China [CARS-36]
Type I interferons (IFNs), predominantly IFN-alpha and beta, 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-beta transcription in MARC-145 cells, and the results showed that the IFN-beta promoter activation could be suppressed by NSP1 alpha, NSP2, NSP1 beta, NSP3, NSP4, NSP5 and NSP11. We next confirmed that the inhibitory effect of NSP4 was mainly mediated through suppressing NF-kappa B activation, whereas not hindering NF-kappa B phosphorylation and nuclear translocation, and nuclear-localized NSP4 was responsible for inhibiting IFN-beta activation. We further found that the NSP4 of different pathogenic PRRSV strains exhibited differential inhibitory effect on IFN-beta, NF-kappa B, 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-beta 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. (C) 2014 Elsevier B.V. All rights reserved.
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