Cytomegalovirus DNA polymerase (UL54) (UL54)

Cytomegalovirus (CMV) DNA polymerase, encoded by the UL54 gene, is a critical enzyme belonging to the Family B DNA polymerases, which are essential for the replication of the viral genome in herpesviruses (UniProt: P06477). The enzyme functions as a DNA-directed DNA polymerase, catalyzing the synthesis of viral DNA by incorporating deoxyribonucleoside triphosphates into the growing chain (PubMed: 11831707). It also possesses a 3'-5' exonuclease domain that provides proofreading capabilities, which is vital for maintaining the genetic integrity of the virus during rapid replication cycles. In clinical settings, this polymerase is the central target for treating infections caused by CMV and other herpesviruses, which can lead to severe morbidity in immunocompromised individuals and neonates (StatPearls: NBK499940). Drugs such as ganciclovir and cidofovir act as competitive inhibitors and DNA chain terminators after being phosphorylated by viral or cellular kinases (PubChem: CID 3454). Foscarnet provides an alternative mechanism by acting as a pyrophosphate analog that directly blocks the pyrophosphate binding site on the polymerase without requiring prior activation. The emergence of drug resistance is a major therapeutic challenge, typically involving point mutations in the UL54 gene that reduce the enzyme's affinity for antiviral agents (PubMed: 15917462).

Other names

DNA-directed DNA polymeraseHerpesvirus family B DNA polymeraseCMV PolUL54 gene product

Competitive inhibition of deoxyribonucleoside triphosphate (dNTP) incorporation and DNA chain termination