猪瘟是猪重要传染病之一，其防控已成为养猪业的重大课题，目前该病的免疫机制和致病机理尚未阐明。抗病毒免疫刺激基因ISG15由I型干扰素（IFN-I）诱导产生，通过类泛素修饰系统标记病毒蛋白发挥抗病毒作用。我们发现猪瘟病毒（CSFV）一方面抑制IFN-I表达，另一方面也引起宿主细胞中ISG15的mRNA水平及蛋白表达量的显著上调，这一现象说明CSFV对 ISG15的调控不受IFN-I直接影响，可通过另外途径进行调节。本项目拟通过研究CSFV蛋白对ISG15分子表达的影响，确定上调ISG15的CSFV蛋白；摸索CSFV蛋白与ISG15分子之间相互调控的主要通路，阐明CSFV感染既可抑制细胞IFN-I的产生，逃逸宿主早期固有免疫应答，又能上调ISG15表达的分子机制；在此基础上进一步摸索ISG15过表达及其ISGylation对CSFV复制转录的影响，为抗病育种或猪瘟免疫新途径提供理论依据。

Classical swine fever (CSF) arise economical lose of thousands millions in China each year. The prevention and control of CSF become a very important research title in pigs industry, due to a little has been known for their immunological and pathogenic mechanisms. Immune stimulated gene ISG15 inducing by type-I interferon (IFN-I) exerts antiviral activity via modification of viral proteins by ubiquitination-like system. We found that classical swine fever virus (CSFV) inhibits IFN-I expression, but significantly up-regulate mRNA level and protein expression of ISG15 in vivo and in vitro, implicating that IFN-I does not involve in regulation between CSFV and ISG15. There may be another alternative pathway for CSFV up-regulate ISG15. To specific this finding, in this study our group attempt to determine which CSFV protein influence on ISG15 expression, elucidate molecular pathway of CSFV up-regulate ISG15-that is the molecular mechanism how CSFV inhibits IFN-I and evades early innate immune response of host, and up-regulation of ISG15, and then further to explore the influence over-expression of ISG15 and its ISGylation on replication and transcription of CSFV. These data will be very helpful for anti-viral diseases breeding or provide new idea for prevention and control of CSFV.