title: MCMV exploits the spleen as a transfer hub for systemic dissemination upon oronasal inoculation.
abstract: Murine cytomegalovirus (MCMV) infection in mice is a commonly used animal model for studying human cytomegalovirus (HCMV) infections. In our previous studies, a mouse model based on an oronasal MCMV infection was set up for mimicking a natural infection, and the spleen was hypothesized to regulate viremia and virus dissemination to distal organs such as submandibular glands. Here, the role of the spleen during an MCMV infection was investigated by the comparison of intact and splenectomized Balb/c mice. Both highly passaged MCMV Smith and low passaged MCMV HaNa1 were used. Various samples were collected at 7, 14, and 21 days post inoculation (dpi) for analyses by virus isolation/titration, co-cultivation and qPCR. The results showed that for both virus strains, 1) cell-associated virus in PBMC (determined by co-cultivation) was detected in intact mice but not in splenectomized mice; 2) the mean viral DNA load in PBMC of splenectomized mice was 4.4-(HaNa1)/2.7-(Smith) fold lower at the peak viremia (7dpi) in contrast to that of intact mice; and 3) infectious virus in the submandibular glands was detected later in splenectomized mice (14dpi) than in intact mice (7dpi). Moreover, the average virus titers in submandibular glands of splenectomized mice were 10-(HaNa1)/7.9-(Smith) fold lower at 14dpi and 1.7-(HaNa1)/2.1-(Smith) fold lower at 21dpi compared with that of intact mice. Upon inoculation with MCMV Smith, infectious virus was found in the kidneys and liver of intact mice, but not in splenectomized mice. Taken together, all these data clearly demonstrate that virus dissemination to distant organs is reduced in splenectomized mice, further confirming the importance of the spleen as a viremia booming site for a natural MCMV infection.
authors.affiliation: Laboratory of Virology, Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Shunchuan
authors.initials: S
authors.lastname: Zhang
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.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Theuns
authors.affiliation: Laboratory of Virology, Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Lowiese M B
authors.initials: LM
authors.lastname: Desmarets
authors.affiliation: Laboratory of Virology, Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Ivan
authors.initials: I
authors.lastname: Trus
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 J
authors.initials: HJ
authors.lastname: Nauwynck
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006566:Herpesviridae Infections / Q000097:blood / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008807:Mice, Inbred BALB C; D009055:Mouth / Q000821:virology; D018146:Muromegalovirus / Q000502:physiology*; D009666:Nose / Q000821:virology; D013154:Spleen / Q000821:virology*; D013156:Splenectomy; D014766:Viremia / Q000821:virology*
keywords: Cell-associated virus; MCMV; Oronasal inoculation; Spleen; Systemic dissemination