Human cytomegalovirus UL54 DNA polymerase (UL54)

Human cytomegalovirus (HCMV) UL54 DNA polymerase is the catalytic subunit of the viral DNA polymerase complex, essential for the replication of the HCMV genome [1, 13]. It possesses 5'-3' polymerase activity for DNA synthesis and 3'-5' exonuclease activity for proofreading, which maintains the integrity of the viral genetic material [4, 10]. For efficient replication, UL54 associates with the processivity factor UL44, which facilitates the synthesis of long DNA strands [1, 11]. This enzyme is the primary target for several key antiviral medications, such as ganciclovir, foscarnet, and cidofovir, which are used to treat HCMV infections in immunocompromised patients and neonates [2, 9]. These drugs function by inhibiting the polymerase's activity or causing premature DNA chain termination [3, 5]. However, the clinical utility of these agents is often limited by the emergence of drug-resistant mutations in the UL54 gene, which can lead to treatment failure and cross-resistance among different classes of antivirals [12, 14].

Other names

pUL54HCMV DNA polymeraseDNA-directed DNA polymerase catalytic subunitPolHuman herpesvirus 5 DNA polymerase

Nucleoside and nucleotide analogs (e.g., ganciclovir, cidofovir) act as competitive inhibitors of natural dNTPs and are incorporated into the viral DNA, leading to chain termination [3, 4]. Pyrophosphate analogs (e.g., foscarnet) non-competitively inhibit the pyrophosphate binding site of the enzyme, preventing the release of pyrophosphate and the addition of new nucleotides [5, 9].