非洲猪瘟病毒
生物
毒力
基因
病毒
病毒学
病毒复制
DNA病毒
遗传学
基因组
作者
Yingnan Liu,Zhou Shen,Zhixun Xie,Yingying Song,Yao Li,Rui Liang,Lang Gong,Dongdong Di,Jianqi Liu,Jingyi Liu,Zongyan Chen,Wanqi Yu,Lu Lv,Qiuping Zhong,Xinxin Liao,Chuanwen Tian,Rongrong Wang,Qing Song,Heng Wang,Guiqing Peng,Hongjun Chen
标识
DOI:10.1073/pnas.2210808120
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-GZΔ I73R 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-GZΔ I73R can be a potent live-attenuated vaccine candidate.
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