Human cytomegalovirus DNA polymerase (UL54)

Human cytomegalovirus (HCMV) DNA polymerase is a vital enzyme responsible for the replication of the viral genome during infection [1, 3]. It consists of a catalytic subunit, encoded by the UL54 gene, and an accessory processivity factor, UL44, which together ensure the efficient synthesis of long DNA strands [1, 4, 7]. As a DNA-directed DNA polymerase, it incorporates deoxynucleoside triphosphates into the growing viral DNA chain and possesses 3'-5' exonuclease activity for proofreading [1]. This enzyme is the primary therapeutic target for treating HCMV infections, particularly in immunocompromised individuals and neonates [2, 7, 9]. Current antiviral drugs such as ganciclovir, foscarnet, and cidofovir inhibit this polymerase by acting as nucleoside analogs that cause chain termination or by blocking the pyrophosphate binding site [1, 6, 13]. Despite their efficacy, these treatments are associated with severe side effects like nephrotoxicity and bone marrow suppression, and their long-term use frequently leads to the development of drug-resistant mutations in the UL54 gene [1, 2, 9, 13].

Other names

UL54pUL54DNA polymerase catalytic subunitDNA-directed DNA polymeraseHHV-5 DNA polymerase

Inhibition of viral DNA synthesis via DNA chain termination (nucleoside/nucleotide analogs) or competitive inhibition of the pyrophosphate binding site (foscarnet) [1, 2, 6, 10, 13].