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 T. Manning, Nantian Lin Harsell, Rebecca S. Cook, Cheng Huang, Janko Nikolich‐Žugich, Tomoko Makishima, Slobodan Paessler
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.