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Journal of Virology, October 1999, p. 8512-8518, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activation of Herpesvirus Gene Expression by the Human Cytomegalovirus Protein pp71

Elizabeth G. Homer,dagger Angela Rinaldi, Mary Jane Nicholl, and Chris M. Preston*

Medical Research Council Virology Unit, Glasgow G11 5JR, Scotland

Received 17 May 1999/Accepted 19 July 1999

The activation of gene expression by the human cytomegalovirus (HCMV) particle was investigated. The HCMV major immediate-early (IE) promoter was cloned upstream of the Escherichia coli lacZ coding sequences, and the resulting cassette was introduced into the genome of a herpes simplex virus type 1 (HSV-1) mutant lacking functional VP16. Upon infection with the HSV-1 recombinant in the presence of cycloheximide, to block de novo protein synthesis, expression of lacZ-specific transcripts was increased by fivefold when HCMV was included in the inoculum. Accumulation of HSV-1 IE RNAs was also stimulated by coinfection with HCMV, as was expression of the adenovirus 5 VAI transcript when the VAI gene was cloned into the HSV-1 genome. Coinfection with HCMV did not alter mRNA stability or uncoating of the HSV-1 genome. The coding sequences for the HCMV phosphoprotein pp71, controlled by the HCMV IE promoter, were cloned into an HSV-1 recombinant impaired for the production of the three major transactivators (VP16, ICP0, and ICP4) to yield a recombinant (in1324) which expressed pp71 but did not cause significant cytotoxicity. Infection with in1324 resulted in stimulation of HCMV IE, HSV-1 IE, and VAI expression, demonstrating that pp71 is responsible for the effects we observed when using the entire HCMV particle. Therefore, HCMV pp71 exhibits novel properties in its ability to stimulate gene expression from a range of promoters present in a herpesvirus genome.

* Corresponding author. Mailing address: Medical Research Council Virology Unit, Church St., Glasgow G11 5JR, Scotland. Phone: 44 141 330 4635. Fax: 44 141 337 2236. E-mail: c.preston{at}vir.gla.ac.uk.

dagger Present address: Department of Medical Oncology, University of Glasgow, CRC Beatson Laboratories, Glasgow G61 1BD, Scotland.

Journal of Virology, October 1999, p. 8512-8518, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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