Affiliation:
1. Department of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Virginia 23298-0163
Abstract
ABSTRACT
Herpesviruses have large double-stranded linear DNA genomes that are formed by site-specific cleavage from complex concatemeric intermediates. In this process, only one of the two genomic ends are formed on the concatemer. Although the mechanism underlying this asymmetry is not known, one explanation is that single genomes are cleaved off of concatemer ends in a preferred direction. This implies that
cis
elements control the direction of packaging. Two highly conserved
cis
elements named
pac1
and
pac2
lie near opposite ends of herpesvirus genomes and are important for cleavage and packaging. By comparison of published reports and by analysis of two additional herpesviruses, we found that
pac2
elements lie near the ends formed on replicative concatemers of four herpesviruses: herpes simplex virus type 1, equine herpesvirus 1, guinea pig cytomegalovirus, and murine cytomegalovirus. Formation of
pac2
ends on concatemers depended on terminal
cis
sequences, since ectopic cleavage sites engineered into the murine cytomegalovirus genome mediated formation of
pac2
ends on concatemers regardless of the orientation of their insertion. These findings are consistent with a model in which
pac2
elements at concatemer ends impart a directionality to concatemer packaging by binding proteins that initiate insertion of concatemer ends into empty capsids.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
34 articles.
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