Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children, accounting for between 20 and 60% of all SNHL. It is estimated that at least 8000 infants born annually in the US will have congenital CMV-induced SNHL, with a significant proportion of these children exhibiting delayed onset and progressive deterioration of hearing after the newborn period. Currently, little is known about the mechanism underlying CMV-induced birth defects. Since in utero CMV infection causes SNHL whereas postnatal infection does not, we postulate that CMV-induced cochlear malformations are caused by viral-induced dysregulation of multiple host (embryonic) cell signaling pathways essential for normal cochlear morphogenesis. Our laboratory has recently developed a novel mouse embryonic organ culture model of CMV-induced cochlear malformations which mimics the pathology seen in children with congenital CMV infection and are using this in vitro embryonic model to study the molecular pathology of the CMV-induced cochlear abnormalities. Long-term, our goal is to identify the molecular mechanisms underlying CMV-induced cochlear dysmorphogenesis and identify key cellular targets against which new cochlear-specific, postnatal therapies can be directed. This is clinically important because the prevalence of CMV-induced SNHL is considerable, present antiviral therapies are teratogenic in themselves, and long-term use of current antiviral drugs by infected children present serious safety concerns.
CMV and Deafness
Legend: mCMV induced numerous supernumerary hair cells in a disorganized arrangement. Hair cells were labeled with an antibody to myosin VIIa (myo, green) and nuclei were stained with DAPI (blue). Controls (A) display 1 inner hair cell (IHC) and 3 outer hair cells (OHCs). mCMV-infection induced a mark increase in hair cell population; these supernumerary hair cells (open arrows) are densely packed and disorganized.
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