A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences
PLoS Biology Pub Date : 2024-11-07 eCollection Date: 2024-11-01 DOI:10.1371/journal.pbio.3002871
Kriti Kestur Biligiri, Nishi Raj Sharma, Abhishek Mohanty, Debi Prasad Sarkar, Praveen Kumar Vemula, Shravanti Rampalli
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Abstract

Protein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in methylation of proteins encoded by viruses and its impact on host-pathogen interactions remain poorly understood. In this study, we discovered distinct nucleo-cytoplasmic form of euchromatic histone methyltransferase 1 (EHMT1N/C), a PKMT, that phase separates into viral inclusion bodies (IBs) upon cytoplasmic RNA-virus infection (Sendai Virus). EHMT1N/C interacts with cytoplasmic EHMT2 and methylates SeV-Nucleoprotein upon infection. Elevated nucleoprotein methylation during infection correlated with coalescence of small IBs into large mature platforms for efficient replication. Inhibition of EHMT activity by pharmacological inhibitors or genetic depletion of EHMT1N/C reduced the size of IBs with a concomitant reduction in replication. Additionally, we also found that EHMT1 condensation is not restricted to SeV alone but was also seen upon pathogenic RNA viral infections caused by Chandipura and Dengue virus. Collectively, our work elucidates a new mechanism by which cytoplasmic EHMT1 acts as proviral host factor to regulate host-pathogen interaction.

EHMT1N 的细胞质形式会使病毒蛋白甲基化,从而使包涵体成熟并高效复制病毒。
蛋白赖氨酸甲基转移酶(PKMTs)对组蛋白和非组蛋白进行甲基化,以调节生物结果,如发育和疾病,包括病毒感染。虽然 PKMTs 通过宿主基因调控抗病毒反应的作用已被广泛研究,但它们在病毒编码蛋白甲基化中的作用及其对宿主-病原体相互作用的影响仍鲜为人知。在这项研究中,我们发现了一种独特的核-细胞质形式的外色素组蛋白甲基转移酶 1(EHMT1N/C),它是一种 PKMT,在细胞质 RNA 病毒(仙台病毒)感染时会相分离成病毒包涵体(IB)。EHMT1N/C 与细胞质 EHMT2 相互作用,并在感染时甲基化 SeV 核蛋白。感染期间核蛋白甲基化的升高与小 IB 聚合成大的成熟平台以进行有效复制有关。通过药物抑制剂或遗传性 EHMT1N/C 基因缺失抑制 EHMT 活性可缩小 IB 的大小,同时减少复制。此外,我们还发现,EHMT1的缩聚不仅限于SeV,在钱迪普拉病毒和登革热病毒引起的致病性RNA病毒感染时也会出现。总之,我们的工作阐明了细胞质 EHMT1 作为病毒宿主因子调节宿主与病原体相互作用的新机制。
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来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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