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

CD4 T 细胞耗竭可预防小鼠模型中拉沙热相关的听力损失

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作者:Junki Maruyama, Rachel A Reyna, Megumi Kishimoto-Urata, Shinji Urata, John T Manning, Nantian Harsell, Rebecca Cook, Cheng Huang, Janko Nikolich-Zugich, 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.

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