title: Difference in replication of low-passage MCMV HaNa1 in BALB/c, C57BL/6 and NOD mice and role of different branches of immunity in susceptibility.
abstract: Currently, murine cytomegalovirus (MCMV) infections have been studied extensively in inbred mice via intraperitoneal route with highly passaged strains. However, the question how a low-passage MCMV replicates in inbred mice via a natural route remained unanswered. Here, different inbred mice (BALB/c, C57BL/6 and NOD) were inoculated oronasally with a low-passage MCMV strain, HaNa1. Viral replication was evaluated by virus titration and quantitative real-time PCR, and antibody response was assessed by immunoperoxidase cell monolayer assay (IPMA). In BALB/c mice, virus persisted in nasal mucosa (from 3 dpi) and submandibular glands (from 7 dpi) until the end of experiment (49 dpi). In C57BL/6 mice, infectious virus was only detected in nasal mucosa from 3 dpi until 21 dpi; viral genome was still detectable in nasal mucosa until 49 dpi. Although infectious virus was not detected in submandibular glands of C57BL/6 mice, viral genome was detected from 7 dpi until 49 dpi. NOD mice appeared to be even more resistant with absence of any productive infection; viral genome was detected at low levels in nasal mucosa. We demonstrated that there was a strong correlation between on the one hand degree of productive replication and on the other hand the time of first appearance and titer of MCMV-specific IgG antibody. The deficiency of functional T and B cells and interleukin-2 (IL-2) common-γ chain (γc) did not increase the susceptibility to MCMV by the use of NOD.SCID and NSG mice. In addition, using monocytic cells from different inbred mice we found patterns of resistance similar to those seen in vivo, as assessed by viral antigen expression. Taken together, these results demonstrated that upon oronasal inoculation low-passage MCMV HaNa1 replication clearly differs between different inbred mice (BALB/c>C57BL/6>NOD); resistance in vivo to MCMV is partly due to less susceptibility of host target cells and is independent of T, B cells and γc signaling cytokine-dependent NK cell activities.
authors.affiliation: Laboratory of Virology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Laboratory of Virology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: Shunchuan.Zhang@ugent.be.
authors.forename: Shunchuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University, Gent, Belgium.
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
authors.affiliation: Laboratory of Virology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: Hans.Nauwynck@ugent.be.
authors.forename: Hans
authors.initials: H
authors.lastname: Nauwynck
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000032:analysis; D004198:Disease Susceptibility; D007963:Leukocytes, Mononuclear / Q000821:virology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018146:Muromegalovirus / Q000254:growth & development* / Q000276:immunology*; D009297:Nasal Mucosa / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction; D013363:Submandibular Gland / Q000821:virology; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral
keywords: Genetic resistance; HaNa1; Inbred mice; Murine cytomegalovirus; Natural infection