PDF(Sci-hub)
Abstract：
The Caprine parainfluenza virus 3 (CPIV3) is a novel Paramyxovirus that is isolated from goats suffering from respiratory diseases. Presently, the pathogenesis of CPIV3 infection has not yet been fully characterized. The Type I interferon (IFN) is a key mediator of innate antiviral responses, as many viruses have developed strategies to circumvent IFN response, whether or how CPIV3 antagonizes type I IFN antiviral effects have not yet been characterized. This study observed that CPIV3 was resistant to IFN-α treatment and antagonized IFN-α antiviral responses on MDBK and goat tracheal epithelial (GTE) cell models. Western blot analysis showed that CPIV3 infection reduced STAT1 expression and phosphorylation, which inhibited IFN-α signal transduction on GTE cells. By screening and utilizing specific monoclonal antibodies (mAbs), three CPIV3 accessory proteins C, V and D were identified during the virus infection process on the GTE cell models. Accessory proteins C and V, but not protein D, was identified to antagonize IFN-α antiviral signaling. Furthermore, accessory protein C, but not protein V, reduced the level of IFN-α driven phosphorylated STAT1 (pSTAT1), and then inhibit STAT1 signaling. Genetic variation analysis to the PIV3 accessory protein C has found two highly variable regions (VR), with VR2 (31-70th aa) being involved in for the CPIV3 accessory protein C to hijack the STAT1 signaling activation. The above data indicated that CPIV3 is capable of inhibiting IFN-α signal transduction by reducing STAT1 expression and activation, and that the accessory protein C, plays vital roles in the immune escape process.
摘要：
山羊副流感病毒3（CPIV3）是一种新型的副粘病毒，分离自患有呼吸道疾病的山羊。目前,CPIV3感染的发病机制尚未完全明确。I型干扰素（IFN）是先天抗病毒反应的关键介质，由于许多病毒已经开发出规避IFN应答的策略，CPIV3是否或如何拮抗I型IFN抗病毒作用尚未被表征。这项研究观察到CPIV3对MDBK和山羊气管上皮（GTE）细胞模型的IFN-α治疗和拮抗IFN-α抗病毒反应具有抗性。Westernblot分析显示CPIV3感染降低了STAT1的表达和磷酸化,从而抑制GTE细胞的IFN-α信号转导。通过筛选和利用特异性单克隆抗体（mAb），三种CPIV3辅助蛋白C，在GTE细胞模型上的病毒感染过程中鉴定出V和D。辅助蛋白C和V,但不是蛋白质D,被鉴定为拮抗IFN-α抗病毒信号。此外，辅助蛋白C,但不是蛋白V,降低IFN-α驱动的磷酸化STAT1（pSTAT1）的水平，然后抑制STAT1信号。对PIV3辅助蛋白C的遗传变异分析发现了两个高度可变区(VR),与VR2（31-70aa）参与CPIV3辅助蛋白C劫持STAT1信号传导激活。以上数据表明，CPIV3能够通过降低STAT1的表达和活化来抑制IFN-α信号转导，辅助蛋白C，在免疫逃逸过程中起着至关重要的作用。
