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

Daniell L. Rowles, Yuan Chin Tsai, Todd M. Greco, Aaron E. Lin, Minghao Li, Justin Yeh, Ileana M. Cristea

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16 引文 斯高帕斯(Scopus)

摘要

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 DNMT3A knockdowns trigger reductions in virus titers. Altogether, our results highlight a functional association of viral proteins with the mammalian DNA methyltransferase machinery, pointing to DNMT3A as a host factor required for effective HSV-1 infection.
原文英語
頁(從 - 到)1968-1982
頁數15
期刊Proteomics
15
發行號12
DOIs
出版狀態已發佈 - 6月 1 2015

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學

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