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严重发热伴血小板减少综合征病毒诱导m6A阅读蛋白YTHDF1的乳酰化以促进病毒复制。

Severe fever with thrombocytopenia syndrome virus induces lactylation of m6A reader protein YTHDF1 to facilitate viral replication.

作者信息

Liu Bingxin, Tian Xiaoyan, Li Linrun, Zhang Rui, Wu Jing, Jiang Na, Yuan Meng, Chen Deyan, Su Airong, Xu Shijie, Wu Zhiwei

机构信息

Center for Public Health Research, Medical School of Nanjing University, Nanjing, People's Republic of China.

Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People's Republic of China.

出版信息

EMBO Rep. 2024 Dec;25(12):5599-5619. doi: 10.1038/s44319-024-00310-7. Epub 2024 Nov 4.

DOI:10.1038/s44319-024-00310-7
PMID:39496835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11624280/
Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging infectious pathogen with a high fatality rate, is an enveloped tripartite segmented single-stranded negative-sense RNA virus. SFTSV infection is characterized by suppressed host innate immunity, proinflammatory cytokine storm, failure of B-cell immunity, and robust viral replication. m6A modification has been shown to play a role in viral infections. However, interactions between m6A modification and SFTSV infection remain poorly understood. Through MeRIP-seq, we identify m6A modifications on SFTSV RNA. We show that YTHDF1 can bind to m6A modification sites on SFTSV, decreasing the stability of SFTSV RNA and reducing the translation efficiency of SFTSV proteins. The SFTSV virulence factor NSs increases lactylation of YTHDF1 and YTHDF1 degradation, thus facilitating SFTSV replication. Our findings indicate that the SFTSV protein NSs induce lactylation to inhibit YTHDF1 as a countermeasure to host's YTHDF1-mediated degradation of m6A-marked viral mRNAs.

摘要

严重发热伴血小板减少综合征病毒（SFTSV）是一种新出现的、致死率高的传染性病原体，是一种有包膜的三分体分段单链负义RNA病毒。SFTSV感染的特征是宿主固有免疫受到抑制、促炎细胞因子风暴、B细胞免疫功能衰竭以及病毒大量复制。m6A修饰已被证明在病毒感染中起作用。然而，m6A修饰与SFTSV感染之间的相互作用仍知之甚少。通过MeRIP-seq，我们鉴定了SFTSV RNA上的m6A修饰。我们发现YTHDF1可以结合SFTSV上的m6A修饰位点，降低SFTSV RNA的稳定性并降低SFTSV蛋白的翻译效率。SFTSV毒力因子NSs增加YTHDF1的乳酸化并导致YTHDF1降解，从而促进SFTSV复制。我们的研究结果表明，SFTSV蛋白NSs诱导乳酸化以抑制YTHDF1，作为宿主YTHDF1介导的m6A标记病毒mRNA降解的应对措施。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33fb/11624280/9e5caafa3c51/44319_2024_310_Fig8_ESM.jpg
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