Human cytomegalovirus terminase subunit pUL56 (pUL56)

The Human cytomegalovirus (HCMV) pUL56 subunit is the large component of the viral DNA terminase complex, which also includes the pUL89 and pUL51 subunits. It plays a critical role in the late stages of the HCMV replication cycle by mediating the cleavage of long, concatemeric viral DNA into unit-length genomes and facilitating their translocation into preformed viral capsids. pUL56 provides the necessary energy for this process through its ATPase activity and is responsible for recognizing specific DNA packaging motifs known as pac sequences. As a therapeutic target, pUL56 is the primary site of action for the antiviral drug letermovir (Prevymis). By binding to pUL56, letermovir inhibits the terminase complex's function, thereby preventing the maturation of infectious virions and halting the viral life cycle. Because this mechanism is distinct from that of traditional DNA polymerase inhibitors like ganciclovir, letermovir is effective against strains resistant to those drugs. However, clinical use is associated with the potential for resistance mutations within the UL56 gene, particularly at highly conserved residues such as codon 325, which can confer high-level resistance to the drug.

Other names

UL56HCMV pUL56Large terminase subunitCytomegalovirus pUL56

Inhibition of the viral DNA terminase complex by binding to the pUL56 subunit, preventing the cleavage and packaging of concatemeric viral DNA into capsids.