Viruses, Vol. 17, Pages 1159: Epitranscriptomic Regulation of Hepatitis B Virus by RNA 5-Methylcytosine: Functions, Mechanisms, and Therapeutic Potential

Viruses doi: 10.3390/v17091159

Authors:
Xuliu Zhou
Yanling Huang
Xueyan Zhang
Wuxiang Guan
Fang Zhang
Haojie Hao

Hepatitis B virus (HBV) remains a major global health challenge, with over 296 million people chronically infected worldwide. Despite the availability of antiviral therapies, a functional cure is rarely achieved, highlighting the need for novel therapeutic strategies. RNA 5-methylcytosine (m5C) is a pivotal epitranscriptomic mark implicated in RNA stability, transport, and translation. Emerging evidence shows that m5C is conserved within HBV RNA and plays critical roles in the viral life cycle. This review provides a comprehensive overview of the molecular mechanisms governing m5C deposition and recognition, summarizes recent advances in m5C biology, and highlights the emerging role of epitranscriptomic m5C regulation in HBV infection. We discuss the identification of HBV-specific m5C sites, the functions of key regulatory enzymes, and their interplay in viral RNA stabilization and evasion of innate immune responses. Interplay between m5C and other RNA modifications—particularly N6-methyladenosine (m6A)—is examined alongside virus-specific m5C regulation in EV71, HIV, HCV, EBV, and SARS-CoV-2. Potential links between m5C dysregulation and HBV-induced hepatocarcinogenesis are outlined, and emerging therapeutic strategies targeting the m5C machinery are highlighted. Together, these insights position the epitranscriptomic landscape as a promising avenue for innovative antiviral strategies.

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Xuliu Zhou www.mdpi.com