Hepatitis B virus (HBV) codon adapts well to the gene expression profile of liver cancer: an evolutionary explanation for HBV's oncogenic role.

Due to the evolutionary arms race between hosts and viruses, viruses must adapt to host translation systems to rapidly synthesize viral proteins. Highly expressed genes in hosts have a codon bias related to tRNA abundance, the primary RNA translation rate determinant. We calculated the relative synonymous codon usage (RSCU) of three hepatitis viruses (HAV, HBV, and HCV), SARS-CoV-2, 30 human tissues, and hepatocellular carcinoma (HCC). After comparing RSCU between viruses and human tissues, we calculated the codon adaptation index (CAI) of viral and human genes. HBV and HCV showed the highest correlations with HCC and the normal liver, while SARS-CoV-2 had the strongest association with lungs. In addition, based on HCC RSCU, the CAI of HBV and HCV genes was the highest. HBV and HCV preferentially adapt to the tRNA pool in HCC, facilitating viral RNA translation. After an initial trigger, rapid HBV/HCV translation and replication may change normal liver cells into HCC cells. Our findings reveal a novel perspective on virus-mediated oncogenesis.