CD4 T-cell depletion prevents Lassa fever associated hearing loss in the mouse model

Junki Maruyama, Rachel A. Reyna, Megumi Kishimoto-Urata, Shinji Urata, John Manning, Nantian Harsell, Rebecca Cook, Cheng Huang, Janko Nikolich-Zugich, Tomoko Makishima, Slobodan Paessler

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Lassa virus (LASV) is the causative agent of Lassa fever (LF), which presents as a lethal hemorrhagic disease in severe cases. LASV-induced hearing loss in survivors is a huge socioeconomic burden, however, the mechanism(s) leading to hearing loss is unknown. In this study, we evaluate in a mouse LF model the auditory function using auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to determine the mechanisms underlying LASV-induced hearing loss. In the process, we pioneered measures of ABR and DPOAE tests in rodents in biosafety level 4 (BSL-4) facilities. Our T cell depletion studies demonstrated that CD4 T-cells play an important role in LASV-induced hearing loss, while CD8 T-cells are critical for the pathogenicity in the acute phase of LASV infection. Results presented in this study may help to develop future countermeasures against acute disease and LASV-induced hearing loss.

Original languageEnglish (US)
Article numbere1010557
JournalPLoS pathogens
Volume18
Issue number5
DOIs
StatePublished - May 2022

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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