NS1-mediated DNMT1 Degradation Regulates Human Bocavirus 1 Replication and RNA Processing

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2024 Nov 14

PMID 39541416

Authors

Shuangkang Qin

Honghe Chen

Chuchu Tian

Zhen Chen

Li Zuo

Xueyan Zhang

Haojie Hao

Fang Huang

Haibin Liu

Xiulian Sun

Wuxiang Guan

Affiliations

Soon will be listed here.

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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