Hepatitis B virus core protein and polymerase (HBcAg/Pol)

The Hepatitis B virus (HBV) core protein and polymerase are two essential viral proteins that work in tandem to facilitate viral replication and persistence (UniProt P03146, P03156). The core protein (HBcAg) is the structural subunit of the viral capsid, responsible for encapsidating the viral pregenomic RNA (pgRNA) and the polymerase enzyme (Wikipedia). The polymerase (P protein) is a multifunctional enzyme that performs reverse transcription, DNA synthesis, and RNA degradation (RNase H activity) to produce the viral DNA genome (PMC 3122608). These proteins are central to the HBV lifecycle, including the formation and maintenance of the covalently closed circular DNA (cccDNA) reservoir in the host cell nucleus. Therapeutically, the polymerase is the target of widely used nucleos(t)ide analogues (NAs) which inhibit DNA synthesis, while the core protein is the target of emerging capsid assembly modulators (CAMs) designed to disrupt viral assembly (PMC 7144870). Furthermore, both proteins are frequently utilized as antigens in therapeutic vaccine candidates aimed at inducing a robust immune response to achieve a functional cure for chronic hepatitis B. As antigens, they are the primary targets of the host's cellular immune response, and their inclusion in therapeutic vaccines is intended to stimulate T-cell activity against infected hepatocytes.

Other names

HBcAgHBV P proteinHepatitis B core antigenHBV reverse transcriptaseCapsid proteinHPHBV polymerasep22Nucleocapsid protein

Nucleoside/nucleotide analogues (NAs) act as chain terminators to inhibit the reverse transcriptase and DNA polymerase activities of the HBV polymerase. Capsid assembly modulators (CAMs) target the core protein to either induce the formation of empty, non-infectious capsids or prevent capsid assembly altogether, thereby blocking the encapsidation of the viral genome and the subsequent steps of replication. Therapeutic vaccines utilize these proteins as antigens to stimulate a T-cell mediated immune response against infected hepatocytes.