PDF(Pubmed)
Abstract：
Severe fever with thrombocytopenia syndrome virus (SFTSV), which has been reported in China, Korea, Japan, Vietnam, and Taiwan, is a causative agent of severe fever thrombocytopenia syndrome. This virus has a high mortality and induces thrombocytopenia and leukocytopenia in humans, cats, and aged ferrets, whereas immunocompetent adult mice infected with SFTSV never show symptoms. Anti-SFTSV antibodies have been detected in several animals-including goats, sheep, cattle, and pigs. However, there are no reports of severe fever thrombocytopenia syndrome in these animals. Previous studies have reported that the nonstructural protein NSs of SFTSV inhibits the type I interferon (IFN-I) response through the sequestration of human signal transducer and activator of transcription (STAT) proteins. In this study, comparative analysis of the function of NSs as IFN antagonists in human, cat, dog, ferret, mouse, and pig cells revealed a correlation between pathogenicity of SFTSV and the function of NSs in each animal. Furthermore, we found that the inhibition of IFN-I signaling and phosphorylation of STAT1 and STAT2 by NSs depended on the binding ability of NSs to STAT1 and STAT2. Our results imply that the function of NSs in antagonizing STAT2 determines the species-specific pathogenicity of SFTSV.
摘要：
严重发热伴血小板减少综合征病毒（SFTSV），这在中国已经有报道，韩国,Japan,越南,台湾,是严重发热血小板减少综合征的病原体。这种病毒具有很高的死亡率，并在人类中引起血小板减少和白细胞减少，猫,和年迈的雪貂，而感染SFTSV的免疫活性成年小鼠从不出现症状。已经在包括山羊在内的几种动物中检测到抗SFTSV抗体，绵羊,牛,和猪。然而,这些动物中没有严重发热血小板减少综合征的报道.先前的研究报道，SFTSV的非结构蛋白NSs通过隔离人信号转导子和转录激活因子（STAT）蛋白来抑制I型干扰素（IFN-I）反应。在这项研究中,比较分析NSs作为人类IFN拮抗剂的功能，猫,狗,雪貂,鼠标,猪细胞揭示了SFTSV的致病性与每只动物中NSs的功能之间的相关性。此外，我们发现,NSs对IFN-I信号传导的抑制以及STAT1和STAT2的磷酸化取决于NSs与STAT1和STAT2的结合能力.我们的结果表明，NSs拮抗STAT2的功能决定了SFTSV的物种特异性致病性。
