Animal Model of Sensorineural Hearing Loss Associated with Lassa Virus Infection

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Abstract
Approximately one third of Lassa virus (LASV) infected patients develop sensorineural hearing loss (SNHL) in the late stages of acute disease or in early convalescence. With 500,000 annual cases of Lassa Fever (LF), LASV is a major cause of hearing loss in endemic regions of West Africa. To date, no animal models exist that depict the human pathology of LF with associated hearing loss. Here, we aimed to develop an animal model to study LASV-induced hearing loss using human isolates from a 2012 Sierra Leone outbreak. We have recently established a murine model for LF that closely mimics many features of human disease. In this model, LASV isolated from a lethal human case was highly virulent while the virus isolated from a non-lethal case elicited mostly mild disease with moderate mortality. More importantly, both viruses were able to induce SNHL in surviving animals. However, utilization of the non-lethal, human LASV isolate allowed us to consistently produce large numbers of survivors with hearing loss. Surviving mice developed permanent hearing loss associated with mild damage to the cochlear hair cells and, strikingly, significant degeneration of the spiral ganglion cells of the auditory nerve. Therefore, the pathological changes in the inner ear of the mice with SNHL supported the phenotypic loss of hearing and provided further insights into the mechanistic cause of LF-associated hearing loss.
Funding Information
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (UC7 5UAI094660)
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (UC7 5UAI094660)
  • HHS | NIH | National Institute on Deafness and Other Communication Disorders (K08DC011540)