DNA methyltransferase DNMT3A associates with viral proteins and impacts HSV-1 infection

Proteomics
Daniell L RowlesIleana M Cristea

Abstract

Viral infections can alter the cellular epigenetic landscape, through modulation of either DNA methylation profiles or chromatin remodeling enzymes and histone modifications. These changes can act to promote viral replication or host defense. Herpes simplex virus type 1 (HSV-1) is a prominent human pathogen, which relies on interactions with host factors for efficient replication and spread. Nevertheless, the knowledge regarding its modulation of epigenetic factors remains limited. Here, we used fluorescently-labeled viruses in conjunction with immunoaffinity purification and MS to study virus-virus and virus-host protein interactions during HSV-1 infection in primary human fibroblasts. We identified interactions among viral capsid and tegument proteins, detecting phosphorylation of the capsid protein VP26 at sites within its UL37-binding domain, and an acetylation within the major capsid protein VP5. Interestingly, we found a nuclear association between viral capsid proteins and the de novo DNA methyltransferase DNA (cytosine-5)-methyltransferase 3A (DNMT3A), which we confirmed by reciprocal isolations and microscopy. We show that drug-induced inhibition of DNA methyltransferase activity, as well as siRNA- and shRNA-mediated D...Continue Reading

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Citations

Oct 27, 2016·Cellular and Molecular Life Sciences : CMLS·Ziqiang WangYaou Zhang
Feb 7, 2017·Molecular & Cellular Proteomics : MCP·Todd M Greco, Ileana M Cristea
Jul 8, 2016·Molecular & Cellular Proteomics : MCP·Paul AshfordMaya Topf
Jul 7, 2017·Journal of Virology·Ryosuke KobayashiYasushi Kawaguchi
Apr 6, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Ziqiang WangWeiren Huang
Dec 5, 2020·Viruses·Yonggang Pei, Erle S Robertson

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