TY - JOUR
T1 - CD4 T-cell depletion prevents Lassa fever associated hearing loss in the mouse model
AU - Maruyama, Junki
AU - Reyna, Rachel A.
AU - Kishimoto-Urata, Megumi
AU - Urata, Shinji
AU - Manning, John T.
AU - Harsell, Nantian
AU - Cook, Rebecca
AU - Huang, Cheng
AU - Nikolich-Zugich, Janko
AU - Makishima, Tomoko
AU - Paessler, Slobodan
N1 - Publisher Copyright: Copyright: © 2022 Maruyama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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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U2 - 10.1371/journal.ppat.1010557
DO - 10.1371/journal.ppat.1010557
M3 - Article
C2 - 35605008
SN - 1553-7366
VL - 18
JO - PLoS pathogens
JF - PLoS pathogens
IS - 5
M1 - e1010557
ER -