Cytomegalovirus DNA terminase complex pUL56 subunit (pUL56)

The pUL56 subunit is the large component of the human cytomegalovirus (HCMV) DNA terminase complex, which also includes pUL89 and pUL51 [1, 11]. It plays a critical role in the late stage of the viral replication cycle by recognizing specific packaging signals (pac motifs) on concatemeric viral DNA and providing the ATPase activity necessary for translocating the DNA into preformed viral capsids [1, 4, 8]. Because this DNA packaging mechanism is unique to viruses and has no human homolog, it is an ideal target for highly specific antiviral therapy [2, 4, 15]. Letermovir, a first-in-class terminase inhibitor, binds to pUL56 to block the cleavage and packaging process, effectively preventing the formation of infectious virions [1, 2, 10]. This target is particularly significant in the management of CMV in transplant recipients, where traditional polymerase inhibitors are often limited by myelotoxicity and nephrotoxicity [2, 14, 18]. Resistance to letermovir primarily arises through specific mutations within the UL56 gene, which can compromise the drug's efficacy [1, 17, 18].

Other names

Large terminase subunitUL56HCMV pUL56pUL56 proteinHuman cytomegalovirus UL56pUL56 subunit

Inhibition of the viral DNA terminase complex by binding to the pUL56 subunit, which prevents the cleavage of concatemeric viral DNA into unit-length genomes and its subsequent packaging into viral capsids.