Human cytomegalovirus DNA terminase complex (HCMV DNA terminase) (HCMV DNA terminase)

The Human cytomegalovirus (HCMV) DNA terminase complex is a vital heterotrimeric enzyme assembly responsible for the final stages of viral maturation (Ligat et al., 2018 [PMID: 29437966]). It is composed of three essential subunits: pUL56 (the large subunit), pUL89 (the small subunit), and pUL51 (the portal-binding subunit) (Borst et al., 2016 [PMID: 27139487]). The complex functions by recognizing concatemeric viral DNA, cleaving it into unit-length genomes via the endonuclease activity of pUL89, and translocating the DNA into preformed capsids using the ATPase activity of pUL56 (Ligat et al., 2018 [PMID: 29437966]). This DNA packaging machinery is highly conserved among herpesviruses but lacks a human homolog, making it an ideal target for highly specific antiviral therapy (Goldner et al., 2011 [PMID: 21788470]). The drug letermovir (Prevymis) is a first-in-class inhibitor that specifically targets the pUL56 subunit, thereby blocking the production of infectious virions (Melendez and Razonable, 2015 [PMID: 26449511]). Clinical use of such inhibitors is primarily for the prophylaxis of HCMV infection in hematopoietic stem cell transplant recipients (Marty et al., 2017 [PMID: 29211658]). Resistance to these drugs typically emerges through specific amino acid substitutions in the pUL56 or pUL89 subunits, which can compromise therapeutic efficacy (Chou, 2020 [PMID: 32690531]).

Other names

HCMV DNA terminase complexpUL56-pUL89-pUL51 complexCytomegalovirus DNA packaging complexUL56-UL89-UL51

Inhibition of the viral DNA terminase complex, specifically the pUL56 subunit, which prevents the cleavage of concatemeric viral DNA and its subsequent packaging into viral capsids (Goldner et al., 2011 [PMID: 21788470]).