Human cytomegalovirus DNA terminase complex subunit UL56 (pUL56) (pUL56)

The Human Cytomegalovirus (HCMV) DNA terminase complex subunit UL56 (pUL56) is a critical component of the viral replication machinery (UniProt P06488). It functions as the large subunit of the terminase complex, which is responsible for the ATP-dependent cleavage of concatemeric viral DNA and its subsequent translocation into preformed pro-capsids (PubMed: 28792871). This process is essential for the production of infectious viral particles. Because this mechanism is unique to herpesviruses and lacks a human homolog, pUL56 represents a highly specific therapeutic target (PubMed: 30135619). The drug Letermovir specifically targets this subunit, disrupting the viral life cycle without affecting host cell DNA processes (FDA Label: Prevymis). Resistance to Letermovir is primarily mediated by point mutations within the UL56 gene, such as C325Y, which can emerge during therapy in immunocompromised patients (PubMed: 31113801).

Other names

UL56HCMV pUL56Large terminase subunitCytomegalovirus UL56 proteinDNA terminase subunit UL56

Letermovir inhibits the viral DNA terminase complex by binding to the pUL56 subunit, thereby preventing the cleavage of concatemeric viral DNA into monomeric genomes and blocking their packaging into mature capsids (PubMed: 28792871, FDA Label: Prevymis).