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Journal of Virology, August 2001, p. 7188-7192, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7188-7192.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Abundant Early Expression of gpUL4 from a Human Cytomegalovirus Mutant Lacking a Repressive Upstream Open Reading Frame

John P. Alderete,dagger Stephanie J. Child, and Adam P. Geballe*

Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, and Departments of Microbiology and Medicine, University of Washington, Seattle, Washington 98115

Received 13 March 2001/Accepted 4 May 2001

The human cytomegalovirus UL4 gene encodes a 48-kDa glycoprotein, expression of which is repressed at the translational level by a short upstream open reading frame (uORF2) within the UL4 transcript leader. Mutation of the uORF2 initiation codon in the viral genome eliminates ribosomal stalling at the uORF2 termination site, resulting in early and abundant gpUL4 protein synthesis. This mutation does not appear to affect viral replication kinetics in human fibroblasts. These results reveal that the unusual uORF2 inhibitory mechanism is a principal determinant of the abundance and timing of gpUL4 expression but is nonessential for replication in cell culture.

* Corresponding author. Mailing address: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North---Mail Stop C2-023, P.O. Box 19024, Seattle, Washington 98109-1024. Phone (206) 667-5122. Fax: (206) 667-6523. E-mail: ageballe{at}fhcrc.org.

dagger Present address: Xenotope Diagnostics, Inc., Stanford, CA 94309-9588.

Journal of Virology, August 2001, p. 7188-7192, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7188-7192.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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