Effects of cytomegalovirus infection on embryogenesis and brain development.

Congenital cytomegalovirus (CMV) infection is a significant cause of brain disorders, such as microcephaly, mental retardation, hearing loss and visual disorders in humans. The type and severity of brain disorder may be dependent on the stage of embryonic development when the congenital infection occurs. Developmental disorders may be associated with the type of embryonic cells to which CMV is susceptible and the effects of the infection on the cellular functions of these cells. Early murine embryos, including embryonic stem (ES) cells, are not susceptible to CMV infection. A part of the embryonic cells acquire susceptibility during early development. Mesenchymal cells are the targets of infection at midgestation, affecting organogenesis of the brain, eyes and oral-facial regions. In contrast to ES cells, neural stem progenitor cells (NSPC) from fetal brains are susceptible to murine CMV (MCMV) infection. The viral infection inhibits proliferation and differentiation of the NSPC to neuronal and glial cells in addition to induction of neuronal cell loss. These cellular events may cause brain malformations, such as microcephaly and polymicrogyria. Furthermore, MCMV persists in neuronal cells in developing brains, presumably resulting in neuronal dysfunction.