Animal model of sensorineural hearing loss associated with Lassa virus infection

Nadezhda E. Yun, Shannon Ronca, Atsushi Tamura, Takaaki Koma, Alexey V. Seregin, Kelly Dineley, Milagros Miller, Rebecca Cook, Naoki Shimizu, Aida G. Walker, Jeanon N. Smith, Joseph N. Fair, Nadia Wauquier, Bayon Bockarie, Sheik Humarr Khan, Tomoko Makishima, Slobodan Paessler

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 regions of West Africa where LF is endemic. 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 nonlethal case elicited mostly mild disease with moderate mortality. More importantly, both viruses were able to induce SNHL in surviving animals. However, utilization of the nonlethal, 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.

Original languageEnglish (US)
Pages (from-to)2920-2927
Number of pages8
JournalJournal of Virology
Volume90
Issue number6
DOIs
StatePublished - 2016

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Lassa virus
Sensorineural Hearing Loss
Lassa Fever
hearing
Virus Diseases
Hearing Loss
Animal Models
animal models
infection
fever
Auditory Hair Cells
Sierra Leone
Spiral Ganglion
Viruses
Cochlear Nerve
Western Africa
Acute Disease
Inner Ear
Disease Outbreaks
acute course

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Animal model of sensorineural hearing loss associated with Lassa virus infection. / Yun, Nadezhda E.; Ronca, Shannon; Tamura, Atsushi; Koma, Takaaki; Seregin, Alexey V.; Dineley, Kelly; Miller, Milagros; Cook, Rebecca; Shimizu, Naoki; Walker, Aida G.; Smith, Jeanon N.; Fair, Joseph N.; Wauquier, Nadia; Bockarie, Bayon; Khan, Sheik Humarr; Makishima, Tomoko; Paessler, Slobodan.

In: Journal of Virology, Vol. 90, No. 6, 2016, p. 2920-2927.

Research output: Contribution to journalArticle

Yun, NE, Ronca, S, Tamura, A, Koma, T, Seregin, AV, Dineley, K, Miller, M, Cook, R, Shimizu, N, Walker, AG, Smith, JN, Fair, JN, Wauquier, N, Bockarie, B, Khan, SH, Makishima, T & Paessler, S 2016, 'Animal model of sensorineural hearing loss associated with Lassa virus infection', Journal of Virology, vol. 90, no. 6, pp. 2920-2927. https://doi.org/10.1128/JVI.02948-15
Yun, Nadezhda E. ; Ronca, Shannon ; Tamura, Atsushi ; Koma, Takaaki ; Seregin, Alexey V. ; Dineley, Kelly ; Miller, Milagros ; Cook, Rebecca ; Shimizu, Naoki ; Walker, Aida G. ; Smith, Jeanon N. ; Fair, Joseph N. ; Wauquier, Nadia ; Bockarie, Bayon ; Khan, Sheik Humarr ; Makishima, Tomoko ; Paessler, Slobodan. / Animal model of sensorineural hearing loss associated with Lassa virus infection. In: Journal of Virology. 2016 ; Vol. 90, No. 6. pp. 2920-2927.
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