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Journal of Virology, August 2001, p. 7592-7601, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7592-7601.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Requirement for Uracil-DNA Glycosylase during the Transition to Late-Phase Cytomegalovirus DNA Replication

Charmain Tan Courcelle,1,dagger Justin Courcelle,2 Mark N. Prichard,3 and Edward S. Mocarski1,*

Department of Microbiology and Immunology, Stanford University, Stanford, California 943051; Department of Biological Sciences, Mississippi State University, Mississippi State, Mississippi 397622; and Aviron Inc., Mountain View, California 940863

Received 31 January 2001/Accepted 4 May 2001

Cytomegalovirus gene UL114, a homolog of mammalian uracil-DNA glycosylase (UNG), is required for efficient viral DNA replication. In quiescent fibroblasts, UNG mutant virus replication is delayed for 48 h and follows the virus-induced expression of cellular UNG. In contrast, mutant virus replication proceeds without delay in actively growing fibroblasts that express host cell UNG. In the absence of viral or host cell UNG expression, mutant virus fails to proceed to late-phase DNA replication, characterized by rapid DNA amplification. The data suggest that uracil incorporated early during wild-type viral DNA replication must be removed by virus or host UNG prior to late-phase amplification and encapsidation into progeny virions. The process of uracil incorporation and excision may introduce strand breaks to facilitate the transition from early-phase replication to late-phase amplification.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305-5124. Phone: (650) 723-6435. Fax: (650) 723-1606. E-mail: mocarski{at}stanford.edu.

dagger Present address: Office of Agricultural Communications, Mississippi State University, Mississippi State, MS 39762.

Journal of Virology, August 2001, p. 7592-7601, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7592-7601.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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