Development of Cytomegalovirus-Mediated Sensorineural Hearing Loss in a Guinea Pig Model

被引:28
作者
Park, Albert H. [1 ]
Gifford, Thomas [1 ]
Schleiss, Mark R. [5 ]
Dahlstrom, Lisa [1 ]
Chase, Shane [2 ]
McGill, Lawrence [3 ]
Li, Wenhua [1 ]
Alder, Stephen C. [4 ]
机构
[1] Univ Utah, Sch Med, Div Otolaryngol Head & Neck Surg, Salt Lake City, UT 84132 USA
[2] Univ Utah, Sch Med, Dept Commun Sci & Disorders, Salt Lake City, UT 84132 USA
[3] Univ Utah, Sch Med, Div Associated Reg & Univ Pathologists, Salt Lake City, UT 84132 USA
[4] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84132 USA
[5] Univ Minnesota, Ctr Infect Dis & Microbiol Translat Res, Div Pediat Infect Dis & Immunol, Rochester, MN USA
关键词
CMV INFECTION; INNER-EAR; DISEASE; VACCINE; LABYRINTHITIS; IMMUNIZATION;
D O I
10.1001/archoto.2009.210
中图分类号
R76 [耳鼻咽喉科学];
学科分类号
100213 ;
摘要
Objective: To develop an animal model for cytomegalovirus (CMV)-induced sensorineural hearing loss. Design: Guinea pig model. Setting: University of Utah otolaryngology research labs. Participants: Thirty-one Hartley guinea pig pups were divided into 4 groups. Group 1 pups were delivered from pregnant dams inoculated with 1 x 10(5) plaque-forming units (PFU) of guinea pig CMV (gpCMV). Group 2 and group 3 pups were delivered from pregnant dams inoculated with higher doses of 2 and 4 x 10(5) PFU of gpCMV, respectively. Group 4 pups, the control group, were delivered from uninoculated dams. Main outcome Measures: All groups underwent weekly auditory brainstem response studies. Six weeks after delivery, the brain, cochlea, salivary glands, lungs, liver, and kidneys were harvested. All tissue except the cochlea was analyzed for histologic evidence of the virus. All tissue underwent polymerase chain reaction (PCR) to detect gpCMV. Results: Seven of the 19 (37%) inoculated pups developed a 30-dB hearing loss; none of the animals in the control group had a worse click threshold than 20 dB. Group I pups demonstrated statistically significant asymmetric hearing loss. All 3 inoculated groups showed evidence of progressive hearing loss over time. The control group did not demonstrate evidence of progressive threshold worsening. The PCR testing detected gpCMV in the cochleas of group 2 and group 3 animals. Conclusions: We have successfully demonstrated elevated auditory brainstem response click thresholds with characteristics of progressive and asymmetric loss that have been reported in clinical reports of congenital CMV infection. We also detected gpCMV via PCR testing in the cochleas of inoculated pups.
引用
收藏
页码:48 / 53
页数:6
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