非洲猪瘟(ASF)是猪的一种具有高度传染性和致死性的烈性传染病，在我国被列为一类动物疫病。ASF基因组有180 kb，可编码150-200种蛋白质，且有一半以上的蛋白功能尚不清楚。由于ASFV 结构复杂，病毒感染和免疫机制不清，所以市场上还没有商品化疫苗。近年来报道ASFV基因缺失疫苗可以提供完全保护作用，因此是目前最具开发潜力的疫苗。
2021年，彭贵青教授团队联合中国农业科学院上海兽医研究所探究了抑制宿主蛋白合成的非洲猪瘟基因，阐明E66L是通过跨膜区（13-34 aa）调控PKR/eIF2α通路来抑制宿主蛋白的翻译（Journal of Virology, 2021）。最新的合作研究成果又揭开了ASFV一层新的面纱：I73R基因在ASFV感染早期定位在细胞核中，发挥核酸结合特性，阻止宿主高GC成分的mRNA出核，从而广泛抑制宿主抗病毒蛋白的合成。体内致病性研究显示，缺失I73R基因的重组病毒具有良好的生物安全性和免疫有效性。上述研究结果为深入理解非洲猪瘟病毒致病性和免疫逃逸机制提供了新的理论基础，为非洲猪瘟缺失疫苗的研发提供了新的思路。
该研究得到国家自然科学基金（32170161；U19A2039；U20A2059；32102652）、国家重点研发专项（2021YFD1801401；2021YFD1801300；2021YFD1800104）、上海市青年科技英才杨帆计划（23YF1457400）、中国农业科学院农业科学技术创新项目（CAAS-ZDRW202203）和中央公益性科研单位基础研究基金（Y2022PT11）等项目资助。上海兽医研究所刘英楠博士和华中农业大学沈洲博士为论文共同第一作者，上海兽医研究所陈鸿军研究员、华中农业大学彭贵青教授和华南农业大学王衡副教授为论文共同通讯作者。
审核人：彭贵青
【英文摘要】
African swine fever virus (ASFV) is a large, double-stranded DNA virus that causes a fatal disease in pigs, posing a threat to the global pig industry. Whereas some ASFV proteins have been found to play important roles in ASFV-host interaction, the functional roles of many proteins are still largely unknown. In this study, we identified I73R, an early viral gene in the replication cycle of ASFV, as a key virulence factor. Our findings demonstrate that pI73R suppresses the host innate immune response by broadly inhibiting the synthesis of host proteins, including antiviral proteins. Crystallization and structural characterization results suggest that pI73R is a nucleic-acid-binding protein containing a Zα domain. It localizes in the nucleus and inhibits host protein synthesis by suppressing the nuclear export of cellular messenger RNA (mRNAs). While pI73R promotes viral replication, the deletion of the gene showed that it is a nonessential gene for virus replication. In vivo safety and immunogenicity evaluation results demonstrate that the deletion mutant ASFV-GZΔI73R is completely nonpathogenic and provides effective protection to pigs against wild-type ASFV. These results reveal I73R as a virulence-related gene critical for ASFV pathogenesis and suggest that it is a potential target for virus attenuation. Accordingly, the deletion mutant ASFV-GZΔI73R can be a potent live-attenuated vaccine candidate
原文链接：https://pubmed.ncbi.nlm.nih.gov/37023125/
https://pubmed.ncbi.nlm.nih.gov/33328305/
