Murine cytomegalovirus M78 protein, a G protein-coupled receptor homologue, is a constituent of the virion and facilitates accumulation of immediate-early viral mRNA

The M78 protein of murine cytomegalovirus exhibits sequence features of a G protein-coupled receptor. It is synthesized with early kinetics, it become s partially colocalized with Golgi markers, and it is incorporated into vir al particles. We have constructed a viral substitution mutant, SMsubM78, wh ich lacks most of the M78 ORF. The mutant produces a reduced yield in cultu red 10.1 fibroblast and IC21 macrophage cell lines. The defect is multiplic ity dependent and greater in the macrophage cell line. Consistent with its growth defect in cultured cells, the mutant exhibits reduced pathogenicity in mice, generating less infectious progeny than wild-type virus in all org ans assayed. SMsubM78 fails to efficiently activate accumulation of the vir al m123 immediate-early mRNA in infected macrophages. M78 facilitates the a ccumulation of the immediate-early mRNA in cycloheximide-treated cells, arg uing that it acts in the absence of de novo protein synthesis. We conclude that the M78 G protein-coupled receptor homologue is delivered to cells as a constituent of the virion, and it acts to facilitate the accumulation of immediate-early mRNA.