title: Animal Model of Sensorineural Hearing Loss Associated with Lassa Virus Infection.
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.
  
  
  OBJECTIVE
  Sensorineural hearing loss is a major complication for LF survivors. The development of a small-animal model of LASV infection that replicates hearing loss and the clinical and pathological features of LF will significantly increase knowledge of pathogenesis and vaccine studies. In addition, such a model will permit detailed characterization of the hearing loss mechanism and allow for the development of appropriate diagnostic approaches and medical care for LF patients with hearing impairment.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA Galveston National Laboratory, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Nadezhda E
authors.initials: NE
authors.lastname: Yun
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Ronca
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tamura
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Koma
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Seregin
authors.affiliation: Metabiota, Washington, DC, USA.
authors.forename: Kelly T
authors.initials: KT
authors.lastname: Dineley
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Milagros
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cook
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Aida G
authors.initials: AG
authors.lastname: Walker
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Jeanon N
authors.initials: JN
authors.lastname: Smith
authors.affiliation: Metabiota, Washington, DC, USA.
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Fair
authors.affiliation: Metabiota, Freetown, Sierra Leone.
authors.forename: Nadia
authors.initials: N
authors.lastname: Wauquier
authors.affiliation: Metabiota, Freetown, Sierra Leone.
authors.forename: Bayon
authors.initials: B
authors.lastname: Bockarie
authors.affiliation: Ministry of Health and Sanitation, Freetown, Sierra Leone.
authors.forename: Sheik Humarr
authors.initials: SH
authors.lastname: Khan
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA tomakish@utmb.edu slpaessl@utmb.edu.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Makishima
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA Galveston National Laboratory, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA tomakish@utmb.edu slpaessl@utmb.edu.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Paessler
mesh_terms: D000818:Animals; D003056:Cochlear Nerve / Q000473:pathology; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D007758:Ear, Inner / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000473:pathology*; D006651:Histocytochemistry; D006801:Humans; D007835:Lassa Fever / Q000150:complications* / Q000453:epidemiology; D007836:Lassa virus / Q000302:isolation & purification; D051379:Mice; D008853:Microscopy; D012807:Sierra Leone / Q000453:epidemiology; D014774:Virulence