Yang Liping, Zhang Yan-Jin
Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
Vet Microbiol. 2017 Sep;209:57-65. doi: 10.1016/j.vetmic.2016.12.036. Epub 2016 Dec 30.
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is activated by myriad cytokines, which are involved in regulation of cell growth, proliferation, differentiation, apoptosis, angiogenesis, immunity and inflammatory response. Because of its significance in immune response, JAK-STAT pathway is often targeted by pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV causes reproductive failure in sows and respiratory disease in pigs of all ages. A typical feature of the immune response to PRRSV infection in pigs is delayed production and low titer of virus neutralizing antibodies, and weak cell-mediated immune response. One of the possible reasons for the weak protective immune response is that PRRSV interferes with cytokine-mediated JAK-STAT signaling. PRRSV inhibits interferon-activated JAK-STAT signaling by blocking nuclear translocation of STAT1 and STAT2. The mechanism is that PRRSV non-structural protein 1β (nsp1β) induces degradation of karyopherin α1 (KPNA1), a critical adaptor in nucleo-cytoplasmic transport. PRRSV also antagonizes IL6-activated JAK-STAT3 signaling via inducing degradation of STAT3. In this review, we briefly introduce JAK-STAT signaling, summarize the PRRSV interference with it, and provide perspective on the perturbation in the context of PRRSV-elicited immune response.
Janus激酶（JAK）-信号转导子和转录激活子（STAT）信号通路可被多种细胞因子激活，这些细胞因子参与细胞生长、增殖、分化、凋亡、血管生成、免疫及炎症反应的调控。由于其在免疫反应中的重要性，JAK-STAT通路常成为包括猪繁殖与呼吸综合征病毒（PRRSV）在内的病原体的攻击目标。PRRSV可导致母猪繁殖障碍及各年龄段猪的呼吸道疾病。猪对PRRSV感染免疫反应的一个典型特征是病毒中和抗体产生延迟且效价低，以及细胞介导的免疫反应较弱。保护性免疫反应较弱的可能原因之一是PRRSV干扰细胞因子介导的JAK-STAT信号传导。PRRSV通过阻断STAT1和STAT2的核转位来抑制干扰素激活的JAK-STAT信号传导。其机制是PRRSV非结构蛋白1β（nsp1β）诱导核质转运关键衔接蛋白核转运蛋白α1（KPNA1）的降解。PRRSV还通过诱导STAT3的降解来拮抗IL6激活的JAK-STAT3信号传导。在本综述中，我们简要介绍JAK-STAT信号传导，总结PRRSV对其的干扰，并在PRRSV引发的免疫反应背景下对这种干扰提供见解。
