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

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2024-11-04 DOI:10.1038/s44319-024-00310-7

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

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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.

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严重发热伴血小板减少综合征病毒诱导 m6A 读取蛋白 YTHDF1 乳化，以促进病毒复制。

严重发热伴血小板减少综合征病毒（SFTSV）是一种致死率很高的新出现的传染性病原体，它是一种有包膜的三方分段单链负义 RNA 病毒。SFTSV 感染的特点是宿主先天性免疫受到抑制、促炎细胞因子风暴、B 细胞免疫失败以及病毒复制旺盛。然而，人们对 m6A 修饰与 SFTSV 感染之间的相互作用仍然知之甚少。我们通过 MeRIP-seq 鉴定了 SFTSV RNA 上的 m6A 修饰。我们发现YTHDF1能与SFTSV上的m6A修饰位点结合，从而降低SFTSV RNA的稳定性并降低SFTSV蛋白的翻译效率。SFTSV毒力因子NSs可增加YTHDF1的乳化和YTHDF1的降解，从而促进SFTSV的复制。我们的研究结果表明，SFTSV蛋白NSs诱导乳酰化以抑制YTHDF1，作为宿主YTHDF1介导的m6A标记病毒mRNA降解的对策。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.