Murine Cytomegalovirus Is Not Restricted to the House Mouse Mus musculus domesticus: Prevalence and Genetic Diversity in the European House Mouse Hybrid Zone

Abstract

ABSTRACTMurine cytomegalovirus (MCMV) is a betaherpesvirus of the house mouse,Mus musculus domesticus. It is a common infectious agent of wild mice and a highly studied pathogen of the laboratory mouse. Betaherpesviruses are specific to their hosts, and it is not known if otherMustaxa carry MCMV or if it is restricted toM. m. domesticus. We sampled mice over a 145-km transect of Bavaria-Bohemia crossing a hybrid zone betweenM. m. domesticusandMus musculus musculusin order to investigate the occurrence of MCMV in twoMussubspecies and to test the limits of the specificity of the virus for its host. We hypothesized that if the two subspecies carry MCMV and if the virus is highly specific to its host, divergent MCMV lineages would have codiverged with their hosts and would have a geographical distribution constrained by the host genetic background. A total of 520 mice were tested by enzyme-linked immunosorbent assay (ELISA) and/or nested PCR targeting the M94 gene. Seropositive and PCR-positive individuals were found in bothMussubspecies. Seroprevalence was high, at 79.4%, but viral DNA was detected in only 41.7% of mice. Sequencing revealed 20 haplotypes clustering in 3 clades that match the host genetic structure in the hybrid zone, showing 1 and 2 MCMV lineages inM. m. domesticusandM. m. musculus, respectively. The estimated time to the most recent common ancestor (1.1 million years ago [Mya]) of the MCMVs matches that of their hosts. In conclusion, MCMV has coevolved with these hosts, suggesting that its diversity in nature may be underappreciated, since other members of the subgenusMuslikely carry different MCMVs.IMPORTANCEMurine cytomegalovirus (MCMV) is a betaherpesvirus of the house mouse,Mus musculus domesticus, an important lab model for human cytomegalovirus (HCMV) infection. The majority of lab studies are based on only two strains of MCMVs isolated fromM. m. domesticus, Smith and K181, the latter derived from repeated passage of Smith in mouse submaxillary glands. The presence of MCMV in other members of theMussubgenus had not even been investigated. By screening mouse samples collected in the European house mouse hybrid zone betweenM. m. domesticusandM. m. musculus, we show that MCMV is not restricted to theM. m. domesticussubspecies and that MCMVs likely codiverged with theirMushosts. Thus, the diversity of MCMV in nature may be seriously underappreciated, since other members of the subgenusMuslikely carry their own MCMV lineages.