NS1-mediated DNMT1 degradation regulates human bocavirus 1 replication and RNA processing.

IF 5.5 1区医学 Q1 MICROBIOLOGY PLoS Pathogens Pub Date : 2024-11-14 DOI:10.1371/journal.ppat.1012682

Shuangkang Qin, Honghe Chen, Chuchu Tian, Zhen Chen, Li Zuo, Xueyan Zhang, Haojie Hao, Fang Huang, Haibin Liu, Xiulian Sun, Wuxiang Guan

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Abstract

Methylation of the DNA genome plays an important role in viral gene inactivation. However, the role of DNA methylation in human bocavirus (HBoV) remains unclear. In this study, the HBoV1 genomic DNA was found extensively methylated at the CHG and CHH sites. Inhibiting DNA methylation with 5-aza-2'-deoxycytidine (DAC) altered the methylation status and reduced viral DNA production, while enhanced the RNA splicing at D1 and D3 sites and the polyadenylation at the proximal polyadenylation site, (pA)p. Knockdown of DNA methyltransferase 1 (DNMT1) had the same effect on viral DNA synthesis and RNA processing as the DAC treatment, indicating that DNMT1 is the major host methyltransferase involved in viral DNA methylation. In addition, the nonstructural protein NS1 promoted DNMT1 degradation through the ubiquitin-proteasome pathway to regulate viral replication and RNA processing. Collectively, the results suggest that DNA methylation and DNMT1 facilitate HBoV replication and are essential for appropriate NS1 localization in the nucleus. DNMT1 degradation through NS1 promotes the virus RNA processing, leading to viral protein expression.

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NS1 介导的 DNMT1 降解调节人类轮状病毒 1 的复制和 RNA 处理。

DNA 基因组的甲基化在病毒基因失活中发挥着重要作用。然而，DNA甲基化在人类轮状病毒（HBoV）中的作用仍不清楚。本研究发现，HBoV1 基因组 DNA 的 CHG 和 CHH 位点存在广泛的甲基化。用 5-aza-2'-deoxycytidine (DAC) 抑制 DNA 甲基化可改变甲基化状态并减少病毒 DNA 的产生，同时增强 D1 和 D3 位点的 RNA 剪接以及近端多聚腺苷酸化位点 (pA)p 的多聚腺苷酸化。敲除 DNA 甲基转移酶 1（DNMT1）对病毒 DNA 合成和 RNA 处理的影响与 DAC 处理相同，表明 DNMT1 是参与病毒 DNA 甲基化的主要宿主甲基转移酶。此外，非结构蛋白 NS1 通过泛素-蛋白酶体途径促进 DNMT1 降解，从而调控病毒复制和 RNA 处理。总之，研究结果表明，DNA甲基化和DNMT1促进了HBoV的复制，并且对NS1在细胞核中的适当定位至关重要。DNMT1 通过 NS1 降解促进病毒 RNA 处理，从而导致病毒蛋白表达。

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来源期刊

PLoS Pathogens MICROBIOLOGY-PARASITOLOGY

自引率

3.00%

发文量

598

期刊介绍： Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.