Restricted infection of murine cytomegalovirus (MCMV) in neonatal mice with MCMV-induced sensorineural hearing loss

J Clin Virol. 2015 Aug:69:138-45. doi: 10.1016/j.jcv.2015.06.083. Epub 2015 Jun 19.

Abstract

Background: Congenital infection with human Cytomegalovirus (HCMV) is known to be a causative agent of sensorineural hearing loss (SNHL).

Objectives: To clarify the nongenetic etiology of SNHL by identifying the Cytomegalovirus (CMV)-infected region in the cochleae.

Study design: We established an animal model of SNHL by injecting neonatal Balb/c mice with intracerebral murine Cytomegalovirus (MCMV) within 24h after delivery.

Results: At 3 weeks of age, unilateral and bilateral SNHL were observed in 24% (5/21) and 29% (6/21) of the mice, respectively. SNHL thereafter progressed, with 79% of mice developing bilateral SNHL by 6 weeks of age. MCMV antigens and DNA were detected in the spiral ganglion, and cells surrounding the meninges and scala tympani at 1 week of age. However, both MCMV antigens and DNA had completely disappeared by 2 weeks of age. It is possible that the MCMV reached the spiral ganglion via cerebrospinal fluid as the result of meningitis, as the stria vascularis was found to be MCMV antigen negative. Myosin VI expression in the outer hair cells was lost at 3 weeks of age. MCMV and myosin VI expression disappeared before and during SNHL progression, respectively.

Conclusions: There was a definite lag time between the period in which MCMV antigens/DNA-positive cells were observed and that in which SNHL developed and myosin VI-negative hair cells were observed. Further study is needed to explore the role of MCMV in the loss of myosin VI expression in the outer hair cells.

Keywords: Animal model; Cytomegalovirus; Hearing loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens, Viral / metabolism
  • Cochlea / immunology
  • Cochlea / physiopathology
  • Cochlea / virology*
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / congenital*
  • Cytomegalovirus Infections / physiopathology*
  • Cytomegalovirus Infections / virology
  • DNA, Viral / analysis
  • Disease Models, Animal
  • Evoked Potentials, Auditory, Brain Stem
  • Hair Cells, Auditory, Outer / metabolism
  • Hearing Loss, Sensorineural / physiopathology
  • Hearing Loss, Sensorineural / virology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Myosin Heavy Chains / metabolism

Substances

  • Antigens, Viral
  • DNA, Viral
  • myosin VI
  • Myosin Heavy Chains