title: Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model.
abstract: Congenital human cytomegalovirus infection is a leading infectious cause of long-term neurodevelopmental sequelae, including mental retardation and hearing defects. Strict species specificity of cytomegaloviruses has restricted the scope of studies of cytomegalovirus infection in animal models. To investigate the pathogenesis of congenital human cytomegalovirus infection, we developed a mouse cytomegalovirus model that recapitulates the major characteristics of central nervous system infection in human infants, including the route of neuroinvasion and neuropathological findings. Following intraperitoneal inoculation of newborn animals with mouse cytomegalovirus, the virus disseminates to the central nervous system during high-level viremia and replicates in the brain parenchyma, resulting in a focal but widespread, non-necrotizing encephalitis. Central nervous system infection is coupled with the recruitment of resident and peripheral immune cells as well as the expression of a large number of pro-inflammatory cytokines. Although infiltration of cellular constituents of the innate immune response characterizes the early immune response in the central nervous system, resolution of productive infection requires virus-specific CD8(+) T cells. Perinatal mouse cytomegalovirus infection results in profoundly altered postnatal development of the mouse central nervous system and long-term motor and sensory disabilities. Based on an enhanced understanding of the pathogenesis of this infection, prospects for novel intervention strategies aimed to improve the outcome of congenital human cytomegalovirus infection are proposed.
authors.affiliation: 1] Department of Histology and Embryology, School of Medicine, University of Rijeka, Rijeka, Croatia [2] Department of Infectious Diseases, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Irena
authors.initials: I
authors.lastname: Slavuljica
authors.affiliation: Department of Histology and Embryology, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Daria
authors.initials: D
authors.lastname: Kveštak
authors.affiliation: 1] Department of Histology and Embryology, School of Medicine, University of Rijeka, Rijeka, Croatia [2] Department of Immunology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Peter Csaba
authors.initials: PC
authors.lastname: Huszthy
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: Kosmac
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Britt
authors.affiliation: Department of Histology and Embryology, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjić
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000821:virology; D002493:Central Nervous System Diseases / Q000151:congenital* / Q000276:immunology* / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice