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Journal of Virology, September 1999, p. 7218-7230, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Deletion of the R78 G Protein-Coupled Receptor Gene from Rat Cytomegalovirus Results in an Attenuated, Syncytium-Inducing Mutant Strain

Patrick S. Beisser, Gert Grauls, Cathrien A. Bruggeman, and Cornelis Vink*

Department of Medical Microbiology, Cardiovascular Research Institute Maastricht, Maastricht University, 6202 AZ Maastricht, The Netherlands

Received 22 January 1999/Accepted 20 May 1999

The rat cytomegalovirus (RCMV) R78 gene belongs to an uncharacterized class of viral G protein-coupled receptor (GCR) genes. The predicted amino acid sequence of the R78 open reading frame (ORF) shows 25 and 20% similarity with the gene products of murine cytomegalovirus M78 and human cytomegalovirus UL78, respectively. The R78 gene is transcribed throughout the early and late phases of infection in rat embryo fibroblasts (REF) in vitro. Transcription of R78 was found to result in three different mRNAs: (i) a 1.8-kb mRNA containing the R78 sequence, (ii) a 3.7-kb mRNA containing both R77 and R78 sequences, and (iii) a 5.7-kb mRNA containing at least ORF R77 and ORF R78 sequences. To investigate the function of the R78 gene, we generated two different recombinant virus strains: an RCMV R78 null mutant (RCMVDelta R78a) and an RCMV mutant encoding a GCR from which the putative intracellular C terminus has been deleted (RCMVDelta R78c). These recombinant viruses replicated with a 10- to 100-fold-lower efficiency than wild-type (wt) virus in vitro. Interestingly, unlike wt virus-infected REF, REF infected with the recombinants develop a syncytium-like appearance. A striking difference between wt and recombinant viruses was also seen in vivo: a considerably higher survival was seen among recombinant virus-infected rats than among RCMV-infected rats. We conclude that the RCMV R78 gene encodes a novel GCR-like polypeptide that plays an important role in both RCMV replication in vitro and the pathogenesis of viral infection in vivo.

* Corresponding author. Mailing address: Department of Medical Microbiology, Maastricht University, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. Phone: 31 43 3876669. Fax: 31 43 3876643. E-mail: kvi{at}lmib.azm.nl.

Journal of Virology, September 1999, p. 7218-7230, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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