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In vitro models of viral-induced congenital deafness
Abstract:
Cytomegalovirus (CMV) infects 1 to 2 percent of liveborn infants in the United States and causes varying degrees of perceptive hearing loss. There are eight reported pathologic studies of temporal bones in CMV-infected neonates. Viral replication occurs in nonsensory endolabyrinthine epithelium, but viral antigen is also found in the organ of Corti and spiral ganglion neurons, and CMV has been cultured from perilymph. Further clinicopathologic correlation is frustrated, since the inner ear cannot be biopsied during life, and the number of temporal bones available for study is limited, owing to the decrease in the number of autopsies being performed. Inoculation of CMV into newborn mice, and extracorporeal preparations of mouse and guinea pig fetal inner ears, either in organ culture or as grafts on chick chorioallantoic membranes, yields viral perilabyrinthitis. The different ultrastructural appearances of CMV replicating in epithelial and mesenchymal cells show that animal CMV replicates in mesenchymal cells and human CMV replicates in epithelial cells of the inner ear. These different ultrastructural patterns indicate that the chromophobe (transitional) cells of the stria vascularis of the guinea pig are of mesenchymal origin.
Insights
Cytomegalovirus (CMV) infection in infants can cause hearing loss. This study used animal models to investigate how CMV affects the inner ear, revealing differences in viral replication between human and animal cells.
Area of Science:
- Otolaryngology
- Virology
- Pathology
Background:
- Cytomegalovirus (CMV) is a common congenital infection affecting 1-2% of liveborn infants in the US.
- CMV infection can lead to sensorineural hearing loss in affected infants.
- Limited clinicopathologic studies exist due to the inability to biopsy the inner ear in vivo and declining autopsy rates.
Purpose of the Study:
- To investigate the pathological mechanisms of human Cytomegalovirus (CMV) in the inner ear.
- To correlate viral replication patterns with ultrastructural cell differences in animal models.
- To understand the cellular origin of stria vascularis cells in the inner ear.
Main Methods:
- Inoculation of CMV into newborn mice.
- Extracorporeal culture of fetal mouse and guinea pig inner ears.
- Grafting of inner ear preparations onto chick chorioallantoic membranes.
- Ultrastructural analysis of viral replication in epithelial and mesenchymal cells.
Main Results:
- Viral replication was observed in nonsensory endolabyrinthine epithelium, organ of Corti, and spiral ganglion neurons in human neonates.
- Animal models (mice, guinea pigs) demonstrated viral perilabyrinthitis following CMV inoculation or inner ear culture.
- Distinct ultrastructural patterns indicated human CMV replicates in epithelial cells, while animal CMV replicates in mesenchymal cells of the inner ear.
- These patterns suggest guinea pig stria vascularis chromophobe cells are of mesenchymal origin.
Conclusions:
- Human CMV targets epithelial cells within the inner ear, contributing to pathology and hearing loss.
- Animal models provide insights into CMV inner ear disease, highlighting species-specific cellular tropism.
- Ultrastructural differences in viral replication aid in understanding cell lineage within the inner ear, specifically the mesenchymal origin of guinea pig stria vascularis chromophobe cells.