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Murine cytomegalovirus(MCMV)Smith strain is widely used in mouse models to study HCMV infections.Due to highly serial passages,MCMV Smith has acquired genetic and biological changes.Therefore,a low passaged strain would be more relevant to develop mouse models.Here,the pathogenesis of an infection with MCMV Smith was compared with that of an infection with a low passaged Belgian MCMV isolate HaNa1 in BALB/c adult mice following oronasal inoculation with either a low(104 TCID50/mouse)or high(106 TCID50/mouse)inoculation dose.Both strains were mainly replicating in nasal mucosa and submandibular glands for one to two months.In nasal mucosa,MCMV was detected earlier and longer(1-49dpi)and reached higher titers with the high inoculation dose compared to the low inoculation dose(14-35dpi).In submandibular glands,a similar finding was observed(high dose: 7-49dpi; low dose: 14-42dpi).In lungs,both strains showed a restricted replication.Only the Smith strain established a low level of productive infection in spleen,liver and kidneys.The infected cells were identified as olfactory neurons and sustentacular cells in olfactory epithelium,macrophages and dendritic cells in NALT,acinar cells in submandibular glands,and macrophages and epithelial cells in lungs for both strains.Antibody analysis demonstrated for both strains that IgG2a was the main detectable antibody subclass.Overall,our results show that significant phenotypic differences exist between the two strains.MCMV HaNa1 has been shown to be interesting for use in mouse models in order to get better insights for HCMV infections in immunocompetent humans.