The role of CMV inflammatory genes in hearing loss.
OBJECTIVE
The purpose of this study is to test the hypothesis that virally encoded immunomodulatory genes play a role in cytomegalovirus (CMV)-related hearing loss.


OBJECTIVE
Cytomegalovirus is the leading cause of infectious-related congenital sensorineural hearing loss worldwide. Unfortunately, little is known about the pathophysiology of CMV-related injury to the developing ear.


METHODS
Viral mutagenesis techniques were developed that allow the deletion of a specific viral immunomodulatory gene, macrophage inflammatory protein (MIP) 1alpha homolog. We assessed the extent to which this gene product contributed to auditory pathologic findings in the guinea pig (GP) model. Eighteen weanling GPs (250-350 g) were used under an Institutional Animal Control and Use Committee-approved protocol. We analyzed preinoculation hearing using auditory brainstem response recordings. Intracochlear inoculations were performed on one group of six GPs with sterile viral media, 6 GPs with wild-type (WT) CMV virus, and 6 GPs with mutant "knockout" (KO) virus (with deleted MIP-1alpha homolog). Auditory brainstem responses were then obtained on postinoculation Days 7, 14, 21, and 28.


RESULTS
There was a significant difference in hearing between the KO group and the WT group, with significantly better hearing in the KO group. A comparison of the KO group to the sham group revealed no significant hearing differences between the groups. The WT group had significant threshold shifts by dose at all frequencies meeting our criteria of hearing loss (>30 dB). There were no statistical differences in the sham or KO group.


CONCLUSIONS
Virally encoded immunomodulatory genes such as MIP-1alpha seem to play a significant role in CMV-related hearing loss. This study is the first demonstration of the role of specific viral immune modulation genes in the in vivo pathogenesis of CMV-induced hearing loss in a relevant animal model.
Schraff
Scott A
SA
Department of Pediatric Otolaryngology-Head and Neck Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. Scott.Schraff@CCHMC.org
Brown
David K
DK
Schleiss
Mark R
MR
Meinzen-Derr
Jareen
J
Greinwald
John H
JH
Choo
Daniel I
DI
D000758:Anesthesia; D000818:Animals; D001299:Audiometry; D001309:Auditory Threshold / Q000502:physiology; D003051:Cochlea / Q000821:virology; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D030781:Organisms, Genetically Modified
D019402:Macrophage Inflammatory Proteins