Recently, a paper entitled “African swine fever virus I73R is a critical virulence-related gene: A potential target for attenuation”has been published by Proceedings of the National Academy of Sciences of the United States of America. The research team from the Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences (SHVRI, CAAS) has identified a critical virulence-related gene, and uncovered the molecular mechanism of inhibiting host antiviral protein synthesis.

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, researchers identified I73R, an early viral gene in the replication cycle of ASFV, as a key virulence factor. 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 mRNAs. While pI73R promotes viral replication, the deletion of the gene showed that it is a non-essential gene for virus replication. In vivo safety and immunogenicity evaluation results demonstrate that the deletion mutant ASFV-GZΔI73R is completely non-pathogenic and provides effective protection to pigs against wild type ASFV. These results reveal that I73R, as a novel virulence-related gene, is 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.

This study was supported by the National Natural Science Foundation of China (Grant No. 32170161, U19A2039, U20A2059 and 32102652), the National Key Research and Development Program of China (Grant No 2021YFD1801401, 2021YFD1801300 and 2021YFD1800104), the Shanghai Sailing Program (23YF1457400), the Agricultural Science and Technology Innovation Program (CAAS-ZDRW202203), and the Central Public-interest Scientific Institution Basal Research Fund (Y2022PT11).

More details can be found at the link below: https://pubmed.ncbi.nlm.nih.gov/37023125/

By Liu Yingnan (liuyingnan@shvri.ac.cn)