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Journal of Virology, February 2000, p. 1587-1592, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Ends on Herpesvirus DNA Replicative Concatemers Contain pac2 cis Cleavage/Packaging Elements and Their Formation Is Controlled by Terminal cis Sequences

Michael A. McVoy,* Daniel E. Nixon, Jay K. Hur, and Stuart P. Adler

Department of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Virginia 23298-0163

Received 13 August 1999/Accepted 25 October 1999

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.

* Corresponding author. Mailing address: Department of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, P.O. Box 980163, Richmond, VA 23298-0163. Phone: (804) 828-0132. Fax: (804) 828-6455. E-mail: mmcvoy{at}hsc.vcu.edu.

Journal of Virology, February 2000, p. 1587-1592, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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