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Published on: June 24, 2025
Macrophage inflammatory proteins in cytomegalovirus-related inner ear injury
Scott A Schraff1, Mark R Schleiss, David K Brown
1Department of Pediatric Otolaryngology-Head and Neck Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. Scott.Schraff@CCHMC.org
Objective:
Inner ear inflammation triggered by CMV infection may play a role in CMV-related auditory pathogenesis. The purpose of the study was to determine if a virally encoded macrophage inflammatory protein played a role in CMV-related hearing loss.
Design:
Mutagenesis was performed with deletion of a guinea pig CMV macrophage inflammatory protein. Intracochlear inoculations were performed on three groups of animals (n = 18). Group 1 received sterile viral media, Group 2 received wild-type CMV virus, and Group 3 received "knockout" (KO) virus with a deleted immunomodulation gene. Baseline and postinoculation ABRs were obtained. ELISA and PCR were performed and temporal bones examined.
Subjects:
Eighteen guinea pigs.
Results:
The KO group had significantly better hearing than the WT group. There were no significant differences between the KO and sham groups. The WT group had significant hearing loss at all frequencies. Inflammation and fibrosis were noted in the WT temporal bones only.
Conclusions:
Virally encoded macrophage inflammatory proteins appear to play a significant role in CMV-related hearing loss.
Insights
Cytomegalovirus (CMV) macrophage inflammatory proteins contribute to CMV-related hearing loss. Deleting these proteins in a guinea pig model significantly improved hearing outcomes, reducing inflammation and fibrosis.
Area of Science:
- Otolaryngology
- Virology
- Immunology
Background:
- Inner ear inflammation from Cytomegalovirus (CMV) infection is implicated in hearing loss.
- The specific role of viral proteins in CMV-induced auditory pathogenesis requires further investigation.
Purpose of the Study:
- To determine if a virally encoded macrophage inflammatory protein contributes to CMV-related hearing loss.
- To investigate the impact of deleting this protein on auditory function and inner ear pathology.
Main Methods:
- Guinea pigs (n=18) were divided into three groups: sterile media, wild-type CMV, and CMV with a deleted macrophage inflammatory protein (knockout, KO).
- Intracochlear inoculations were performed, followed by auditory brainstem response (ABR) testing, ELISA, PCR, and temporal bone examination.
Main Results:
- The KO group exhibited significantly better hearing compared to the wild-type (WT) CMV group.
- No significant hearing differences were observed between the KO and sham groups.
- WT CMV infection led to significant hearing loss across all frequencies, accompanied by inflammation and fibrosis in temporal bones.
Conclusions:
- Virally encoded macrophage inflammatory proteins play a significant role in CMV-related hearing loss.
- Targeting these viral proteins may offer a therapeutic strategy for preventing CMV-induced hearing impairment.
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