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

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

Additional file 1: of Interferon gamma protects neonatal neural stem/progenitor cells during measles virus infection of the brain

Figure S1. Representative flow cytometry plots for neural cell identification. Brain homogenates from neonatal mice were analyzed via flow cytometry. Representative plots for each IgG isotype control and the respective neural cell antibody are shown. Top row: Forward/side scatter and 7-AAD negative (−) gates were applied to all samples. 2nd row: Markers for neural stem cells (nestin) and early neuronal markers (doublecortin, DCX). 3rd row: Markers for early neurons (CD24) and for mature neurons (NeuN). 4th Row: Markers for early glial progenitors (A2B5) and mature astrocytes (GFAP). (PDF 504 kb