Human intracellular DNA polymerases (Pol alpha, Pol delta, and Pol epsilon) (Pol alpha, Pol delta, Pol epsilon)

Human Papillomavirus (HPV) is a double-stranded DNA virus that lacks its own DNA polymerase, making it entirely dependent on the host cell's replication machinery for genome duplication (Melendy et al., 1995; NIH, 2014). The virus utilizes its E1 helicase and E2 regulatory protein to recruit specific human intracellular DNA polymerases—primarily DNA polymerase alpha (Pol alpha), delta (Pol delta), and epsilon (Pol epsilon)—to the viral origin of replication (Melendy et al., 1995; Antiva Biosciences, 2023). These enzymes are essential for both the initial amplification of the viral episome and its maintenance during persistent infection (NIH, 2014). Because these host polymerases are required by all HPV genotypes, they represent a broad-spectrum therapeutic target for treating HPV-related conditions, including cervical intraepithelial neoplasia (CIN) and various cancers (Antiva Biosciences, 2023). Drugs such as ABI-2280 (a prodrug of PMEG) are designed to inhibit these polymerases, leading to the termination of viral DNA synthesis and the induction of apoptosis in infected cells (Antiva Biosciences, 2023; Andrei et al., 2014). This host-targeting strategy aims to provide a high barrier to viral resistance compared to drugs targeting specific viral proteins (Antiva Biosciences, 2023).

Other names

Host DNA replication machineryHuman DNA-directed DNA polymerasesDNA polymerase alpha-primase complexPol alphaPol deltaPol epsilon

Competitive inhibition of dNTP incorporation and DNA chain termination (Antiva Biosciences, 2023; Andrei et al., 2014).