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NS1-mediated DNMT1 degradation regulates human bocavirus 1 replication and RNA processing
Shuangkang Qin1,2, Honghe Chen1, Chuchu Tian1
1Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
Plos Pathogens
|November 14, 2024
Summary
DNA methylation, particularly by DNMT1, is crucial for human bocavirus (HBoV) replication and gene expression. Viral protein NS1 degrades DNMT1, promoting viral RNA processing and protein production.
Area of Science:
- Virology
- Epigenetics
- Molecular Biology
Background:
- DNA methylation is vital for viral gene inactivation.
- The specific role of DNA methylation in human bocavirus (HBoV) is not well understood.
Purpose of the Study:
- To investigate the role of DNA methylation and DNMT1 in HBoV replication and RNA processing.
- To elucidate the mechanism by which HBoV regulates viral replication and gene expression through epigenetic modifications.
Main Methods:
- Treatment with 5-aza-2'-deoxycytidine (DAC) to inhibit DNA methylation.
- Knockdown of DNA methyltransferase 1 (DNMT1).
- Analysis of viral DNA production, RNA splicing, and polyadenylation.
- Investigation of the interaction between HBoV NS1 protein and DNMT1.
Main Results:
- HBoV1 genomic DNA showed extensive methylation at CHG and CHH sites.
- Inhibition of DNA methylation (DAC) or DNMT1 knockdown reduced viral DNA production.
- DAC treatment and DNMT1 knockdown enhanced RNA splicing and polyadenylation.
- HBoV nonstructural protein NS1 promotes DNMT1 degradation via the ubiquitin-proteasome pathway.
- DNA methylation and DNMT1 facilitate HBoV replication and NS1 nuclear localization.
Conclusions:
- DNA methylation, mediated by DNMT1, is essential for efficient HBoV replication.
- NS1-induced DNMT1 degradation is a key mechanism for regulating viral RNA processing and protein expression.
- Epigenetic regulation by DNA methylation plays a significant role in the HBoV life cycle.
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