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圖1 ASFV I73R抑制宿主蛋白合成的示意圖

該研究得到國(guó)家自然科學(xué)基金（32170161；U19A2039；U20A2059；32102652）、國(guó)家重點(diǎn)研發(fā)專(zhuān)項(xiàng)（2021YFD1801401；2021YFD1801300；2021YFD1800104）、上海市青年科技英才楊帆計(jì)劃（23YF1457400）、中國(guó)農(nóng)業(yè)科學(xué)院農(nóng)業(yè)科學(xué)技術(shù)創(chuàng)新項(xiàng)目（CAAS-ZDRW202203）和中央公益性科研單位基礎(chǔ)研究基金（Y2022PT11）等項(xiàng)目資助。上海獸醫(yī)研究所劉英楠博士和華中農(nóng)業(yè)大學(xué)沈洲博士為論文共同第一作者，上海獸醫(yī)研究所陳鴻軍研究員、華中農(nóng)業(yè)大學(xué)彭貴青教授和華南農(nóng)業(yè)大學(xué)王衡副教授為論文共同通訊作者。

審核：彭貴青

【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

原文鏈接：https://pubmed.ncbi.nlm.nih.gov/37023125/

https://pubmed.ncbi.nlm.nih.gov/33328305/