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Hepatitis B virus (HBV) infections are the leading cause of chronic hepatitis, which may lead to cirrhosis and hepatocellular carcinoma. Dr. Kevin Tsai’s team at the Institute of Biomedical Sciences found that the RNA of Hepatitis B viruses (HBV) are enriched with small chemical modifications, shedding new light on the molecular mechanisms of HBV replication, one of the leading causes of liver cirrhosis and cancer. Among the viral RNA modifications found, the cytidine methylation 5-methylcytidine (m5C) was found on viral RNAs at 11x higher amounts than on cellular messenger RNAs. Viral m5C is deposited by the cellular enzyme NSUN2 and removal of NSUN2 resulted in a loss of m5C from viral RNAs and failure in the production of viral structural proteins and genomic DNA.

This research uncovered a host-aided RNA modification required for the production of infectious viral particles, suggesting a unique mechanism that may be used as an antiviral target. This research also in collaboration with Professor Chiaho Shih at China Medical University, Assistant Professor Miao-Hsia Lin and the Academician Pei-Jer Chen at the College of Medicine of National Taiwan University. This work was published in the Proceedings of the National Academy of Sciences (PNAS) of the United States, on June 3, 2024.