Hepatitis B virus covalently closed circular DNA-derived messenger RNAs (HBV cccDNA-derived mRNAs)

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA)-derived messenger RNAs are the primary transcripts generated from the viral genome's persistent nuclear reservoir in infected hepatocytes (PubMed: 32634353). These transcripts include the 3.5kb pregenomic RNA (pgRNA) and various subgenomic RNAs (2.4kb, 2.1kb, and 0.7kb), which collectively encode all essential viral proteins, including the surface antigens (HBsAg), core protein (HBcAg), polymerase, and X protein (NIH: PMC7345610). The pgRNA is particularly critical as it serves as the template for reverse transcription to produce new viral DNA genomes (PubMed: 31503353). Because current nucleos(t)ide analogs only inhibit the reverse transcription step and do not eliminate the cccDNA or its transcripts, targeting these mRNAs with RNA interference (RNAi) or antisense oligonucleotides (ASOs) is a major focus for achieving a functional cure (Nature Reviews Gastroenterology & Hepatology, 2020). These therapies, such as Bepirovirsen and JNJ-3989, aim to degrade the viral RNA, thereby reducing the expression of immunosuppressive viral proteins like HBsAg and halting the viral life cycle (PubMed: 34161773).

Other names

HBV transcriptsHBV messenger RNAsHepatitis B virus RNAsHBV pgRNA and subgenomic RNAsPregenomic RNASubgenomic RNAs

Degradation of viral mRNA transcripts via RNA interference (RNAi) or antisense oligonucleotide (ASO) mediated RNase H cleavage, leading to reduced viral protein production and inhibition of replication.