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
AU - Harsell, Nantian
AU - Cook, Rebecca
AU - Huang, Cheng
AU - Nikolich-Zugich, Janko
AU - Makishima, Tomoko
AU - Paessler, Slobodan
N1 - Funding Information:
This research was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases (SP and TM: R01AI129198, SP: U01AI151801, JM: K99AI156012), Japan Society for the Promotion of Science (JM: Overseas Research Fellowships 20170296), Institute for Human Infections and Immunity, University of Texas Medical Branch (TM), Seinsheimer Endowment for Research in the Department of Otolaryngology, University of Texas Medical Branch (TM), and John S. Dunn Foundation (SP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank all the staff of the Animal Resources Center (ARC) and the Histopathology Core at the University of Texas Medical Branch.
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
AN - SCOPUS:85131457422
SN - 1553-7366
VL - 18
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 5
M1 - e1010557
ER -