Immunobiology of congenital cytomegalovirus infection of the central nervous system--the murine cytomegalovirus model

• Published in: Cellular & molecular immunology 2015-03, Vol.12 (2), p.180-191
• Main Authors: Slavuljica, Irena, Kveštak, Daria, Csaba Huszthy, Peter, Kosmac, Kate, Britt, William J, Jonjić, Stipan
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Animals, Newborn - virology; Antibodies; Biomedical and Life Sciences; Biomedicine; CD8 antigen; Central nervous system; Central Nervous System Diseases - congenital; Central Nervous System Diseases - immunology; Central Nervous System Diseases - virology; Complications; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus Infections - congenital; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - virology; Disease Models, Animal; Encephalitis; Human cytomegalovirus; Humans; Immunology; Infections; Inflammation; Innate immunity; Inoculation; Intellectual disabilities; Invasiveness; Lymphocytes T; Medical Microbiology; Mice; Microbiology; Murine cytomegalovirus; Nervous system; Parenchyma; Pathogenesis; Review; Vaccine; Viremia; 中枢神经系统; 先天性; 免疫生物学; 动物模型; 小鼠; 巨细胞病毒; 物种特异性; 病毒感染
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2014.51

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.