Hepatitis B virus pregenomic RNA (HBV pgRNA)

Hepatitis B virus pregenomic RNA (pgRNA) is a 3,200–3,300 nucleotide, terminally redundant RNA transcript produced from the nuclear cccDNA of HBV[2][4][9]. Its most critical roles are (1) acting as the template for reverse transcription to generate new HBV DNA genomes within cytoplasmic nucleocapsids and (2) serving as bicistronic mRNA encoding the core (capsid) and viral polymerase proteins[3][4][7][8][11]. pgRNA contains essential structural elements, including the stem-loop epsilon (ε) domain at the 5′ end, which is recognized by the polymerase and triggers nucleocapsid assembly and genome packaging[3][9][8]. Levels of HBV pgRNA in serum and hepatocytes are emerging as important biomarkers for monitoring chronic HBV infection and antiviral therapy responses[6][10]. Major antiviral drugs against HBV (e.g., nucleos(t)ide analogues) inhibit the reverse transcription step, but pgRNA persists if cccDNA remains active, marking ongoing infection. Modulation of pgRNA encapsidation, RNA structure (including m6A modifications), and stability are active areas of therapeutic research[3][5][13].

Other names

pgRNAHBV pgRNAHBV pregenomeHBV RNAHepatitis B virus pgRNA

Inhibition of reverse transcription (nucleos(t)ide analogues bind polymerase, blocking conversion of pgRNA to DNA); Disruption of nucleocapsid assembly or RNA encapsidation (capsid assembly modulators); Degradation or blockade of pgRNA (experimental antisense/siRNA strategies)