Human cytomegalovirus DNA polymerase catalytic subunit (pUL54) (pUL54)

Human cytomegalovirus (HCMV) DNA polymerase catalytic subunit (pUL54) is a 1242-amino-acid protein essential for viral genome replication (UniProt P08546). It functions as part of a holoenzyme complex, interacting with the processivity factor UL44 to synthesize long concatemeric DNA during the lytic phase of infection (NIH, 1.1.1). HCMV, also known as Human Herpesvirus 5, is a significant pathogen in immunocompromised individuals, such as transplant recipients and HIV/AIDS patients, where it can cause life-threatening conditions like pneumonia, retinitis, and gastrointestinal disease (NIH, 1.4.4). pUL54 is the primary target for several FDA-approved antiviral drugs, including ganciclovir, cidofovir, and foscarnet (NIH, 1.2.1). Ganciclovir and cidofovir are nucleoside/nucleotide analogs that act as competitive inhibitors and DNA chain terminators, while foscarnet is a pyrophosphate analog that blocks the enzyme's pyrophosphate binding site (NIH, 1.1.2). The clinical use of these agents is often complicated by severe side effects, such as nephrotoxicity and myelosuppression, and the emergence of drug-resistant viral strains carrying mutations in the UL54 gene (MDPI, 1.2.2; NIH, 1.2.4).

Other names

UL54HFLF2DNA-directed DNA polymerase catalytic subunitPolHCMV DNA polymeraseHuman cytomegalovirus DNA polymerase

Competitive inhibition of DNA polymerase and DNA chain termination (nucleoside/nucleotide analogs); noncompetitive inhibition of DNA polymerase by binding to the pyrophosphate binding site (pyrophosphate analogs).