Premium
Human cytomegalovirus terminase as a target for antiviral chemotherapy
Author(s) -
Bogner Elke
Publication year - 2002
Publication title -
reviews in medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.06
H-Index - 90
eISSN - 1099-1654
pISSN - 1052-9276
DOI - 10.1002/rmv.344
Subject(s) - capsid , dna , biology , foscarnet , concatemer , virology , dna replication , microbiology and biotechnology , human cytomegalovirus , cleavage (geology) , dna binding protein , genome , genetics , virus , ganciclovir , gene , paleontology , fracture (geology) , transcription factor
Herpesviral DNA packaging is a complex process involving binding and cleavage of DNA containing the specific DNA‐packaging motifs, pac1 and pac2 , and packaging of the resulting unit‒length genomes into preformed procapsids. This process is believed to be mediated by two packaging proteins, the terminase subunits. In the case of human cytomegalovirus the terminase consists of the proteins pUL56 and pUL89. While pUL56 (i) mediates the specific binding to pac sequences on the concatamers, (ii) provides energy for the translocation of the DNA to the procapsids and (iii) associates itself with the capsid for enabling the entry of the DNA into the procapsid, pUL89 is mainly required to effect DNA cleavage. Based on the limited efficacy of the current drugs ganciclovir, cidofovir and foscarnet, new antiviral therapeutics appear to be in demand. Inhibitors targeting pUL56 and/or pUL89 may offer an attractive alternative since mammalian cell DNA replication does not involve cleavage of concatameric DNA. Drugs targeted to terminase‐like proteins should therefore be safe and highly selective. Copyright © 2002 John Wiley & Sons, Ltd.