Key Laboratory of Bioengineering & Biotechnology of the National Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China.
College of Life Science and Engineering, Northwest Minzu University, Lanzhou, 730030, China.
Virus Genes. 2021 Feb;57(1):60-71. doi: 10.1007/s11262-020-01811-y. Epub 2021 Jan 3.
Peste des petits ruminants virus (PPRV) causes an acute and highly contagious disease in domestic and wild small ruminants throughout the world, mainly by invoking immunosuppression in its natural hosts. It has been suggested that the non-structural C protein of PPRV helps in evading host responses but the molecular mechanisms by which it antagonizes the host responses have not been fully characterized. Here, we report the antagonistic effect of PPRV C protein on the expression of interferon-β (IFN-β) through both MAVS and RIG-I mediated pathways in vitro. Dual luciferase reporter assay and direct expression of IFN-β mRNA analysis indicated that PPRV C significantly down regulates IFN-β via its potential interaction with MAVS and RIG-I signaling molecules. Results further indicated that PPRV C protein significantly suppresses endogenous and exogenous IFN-β-induced anti-viral effects in PPRV, EMCV and SVS infections in vitro. Moreover, PPRV C protein not only down regulates IFN-β but also the downstream cytokines of interferon stimulated genes 56 (ISG56), ISG15, C-X-C motif chemokine (CXCL10) and RIG-I mediated activation of IFN promoter elements of ISRE and NF-κB. Further, this study deciphers that PPRV C protein could significantly inhibit the phosphorylation of STAT1 and interferes with the signal transmission in JAK-STAT signaling pathway. Collectively, this study indicates that PPRV C protein is important for innate immune evasion and disease progression.
小反刍兽疫病毒（PPRV）在全球范围内引起家养和野生小反刍动物的急性和高度传染性疾病，主要通过在其自然宿主中引发免疫抑制。有人提出，PPRV 的非结构 C 蛋白有助于逃避宿主反应，但它拮抗宿主反应的分子机制尚未完全阐明。在这里，我们报告了 PPRV C 蛋白通过 MAVS 和 RIG-I 介导的途径在体外对干扰素-β（IFN-β）表达的拮抗作用。双荧光素酶报告基因检测和 IFN-β mRNA 的直接表达分析表明，PPRV C 通过其与 MAVS 和 RIG-I 信号分子的潜在相互作用，显著下调 IFN-β。结果进一步表明，PPRV C 蛋白在 PPRV、EMCV 和 SVS 感染的体外实验中显著抑制内源性和外源性 IFN-β 诱导的抗病毒作用。此外，PPRV C 蛋白不仅下调 IFN-β，还下调干扰素刺激基因 56（ISG56）、ISG15、C-X-C 基序趋化因子（CXCL10）和 RIG-I 介导的 IFN 启动子元件 ISRE 和 NF-κB 的下游细胞因子。此外，本研究揭示 PPRV C 蛋白可显著抑制 STAT1 的磷酸化并干扰 JAK-STAT 信号通路中的信号转导。总之，本研究表明 PPRV C 蛋白对于先天免疫逃避和疾病进展很重要。
