Nj. Davispoynter et al., IDENTIFICATION AND CHARACTERIZATION OF A G-PROTEIN-COUPLED RECEPTOR HOMOLOG ENCODED BY MURINE CYTOMEGALOVIRUS, Journal of virology, 71(2), 1997, pp. 1521-1529
This report describes the identification of a murine cytomegalovirus (
MCMV) G protein-coupled receptor (GCR) homolog. This open reading fram
e (M33) is most closely related to, and collinear with, human cytomega
lovirus UL33, and homologs are also present in human herpesvirus 6 and
7 (U12 for both viruses). Conserved counterparts in the sequenced alp
ha- or gammaherpesviruses have not been identified to date, suggesting
that these genes encode proteins which are important for the biologic
al characteristics of betaherpesviruses. We have detected transcripts
for both UL33 and M33 as early as 3 or 4 h postinfection, and these re
appear at late times. In addition, we have identified N-terminal splic
ing for both the UL33 and M33 RNA transcripts. For both open reading f
rames, splicing results in the introduction of amino acids which are h
ighly conserved among known GCRs. To characterise the function of the
M33 in the natural host, two independent MCMV recombinant viruses were
prepared, each of which possesses an M33 open reading frame which has
been disrupted with the beta-galactosidase gene. While the recombinan
t M33 null viruses showed no phenotypic differences in replication fro
m wild-type MCMV in primary mouse embryo fibroblasts in vitro, they sh
owed severely restricted growth in the salivary glands of infected mic
e. These data suggest that M33 plays an important role in vivo, in par
ticular in the dissemination to or replication in the salivary gland,
and provide the first evidence for the function of a viral GCR homolog
in vivo.