Cytomegalovirus DNA polymerase catalytic subunit (UL54) (UL54)

Cytomegalovirus DNA polymerase catalytic subunit (UL54) is a critical enzyme responsible for the replication of the human cytomegalovirus (HCMV) genome during the late phase of infection. It functions as the catalytic core of the viral DNA replication complex, working in tandem with the processivity factor UL44 to synthesize long concatemeric DNA strands. In addition to its polymerase activity, UL54 possesses 3'-5' exonuclease activity, which provides a proofreading mechanism to ensure high-fidelity replication. HCMV is a significant pathogen that causes severe opportunistic infections, such as retinitis and pneumonia, in immunocompromised individuals and is a leading cause of congenital defects. UL54 is the primary target for several key antiviral drugs, including ganciclovir, foscarnet, and cidofovir, which inhibit viral DNA synthesis through competitive inhibition or by acting as chain terminators. However, prolonged treatment often leads to the emergence of drug-resistant mutations within the UL54 gene, posing a major challenge in clinical management.

Other names

HCMV DNA polymeraseUL54 proteinDNA polymerase catalytic subunitpUL54Human cytomegalovirus DNA polymerase

Inhibition of viral DNA synthesis through competitive inhibition of deoxynucleoside triphosphate binding and DNA chain termination (nucleoside/nucleotide analogs) or by binding to the pyrophosphate binding site (pyrophosphate analogs).