Deletions of MGF110-9L and MGF360-9L from African swine fever virus are highly attenuated in swine and confer protection against homologous challenge

文献类型： 外文期刊

第一作者： Li, Dan

作者： Li, Dan;Ren, Jingjing;Zhu, Guoqiang;Wu, Panxue;Yang, Wenping;Ru, Yi;Feng, Tao;Liu, Huanan;Zhang, Jing;Peng, Jiangling;Tian, Hong;Liu, Xiangtao;Zheng, Haixue

作者机构：

期刊名称：JOURNAL OF BIOLOGICAL CHEMISTRY （ 影响因子：4.8； 五年影响因子：4.8 ）

ISSN：

年卷期： 2023 年 299 卷 6 期

页码：

收录情况： SCI

摘要： African swine fever, caused by a large icosahedral DNA virus (African swine fever virus, ASFV), is a highly contagious disease in domestic and feral swine, thus posing a significant economic threat to the global swine industry. Currently, there are no effective vaccines or the available methods to control ASFV infection. Attenuated live viruses with deleted virulence factors are considered to be the most promising vaccine candidates; however, the mechanism by which these attenuated viruses confer protection is unclear. Here, we used the Chinese ASFV CN/GS/2018 as a backbone and used homologous recombina-tion to generate a virus in which MGF110-9L and MGF360-9L, two genes antagonize host innate antiviral immune response, were deleted (ASFV-AMGF110/360-9L). This genetically modified virus was highly attenuated in pigs and provided effective protection of pigs against parental ASFV challenge. Importantly, we found ASFV-AMGF110/360-9L infection induced higher expression of Toll-like receptor 2 (TLR2) mRNA compared with parental ASFV as determined by RNA-Seq and RT-PCR analysis. Further immunoblotting results showed that parental ASFV and ASFV-AMGF110/360-9L infection inhibited Pam3CSK4-triggered activating phosphor-ylation of proinflammatory transcription factor NF-KB subunit p65 and phosphorylation of NF-KB inhibitor IKBa levels, although NF-KB activation was higher in ASFV-AMGF110/360-9L-infected cells compared with parental ASFV-infected cells. Additionally, we show overexpression of TLR2 inhibited ASFV replication and the expression of ASFV p72 protein, whereas knockdown of TLR2 had the opposite effect. Our findings suggest that the attenuated virulence of ASFV-AMGF110/360-9L might be mediated by increased NF-KB and TLR2 signaling.

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