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Depletion of CD4 and CD8 T Cells Reduces Acute Disease and Is Not Associated with Hearing Loss in ML29-Infected STAT1-/- Mice

Lassa virus (LASV) is a zoonotic virus endemic to western Africa that can cause a potentially lethal and hemorrhagic disease, Lassa fever (LF). Survivors suffer a myriad of sequelae, most notably sudden onset sensorineural hearing loss (SNHL), the mechanism of which remains unclear. Unfortunately, s...

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Autores principales: Reyna, Rachel A., Maruyama, Junki, Mantlo, Emily K., Manning, John T., Taniguchi, Satoshi, Makishima, Tomoko, Lukashevich, Igor S., Paessler, Slobodan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598517/
https://www.ncbi.nlm.nih.gov/pubmed/36289695
http://dx.doi.org/10.3390/biomedicines10102433
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author Reyna, Rachel A.
Maruyama, Junki
Mantlo, Emily K.
Manning, John T.
Taniguchi, Satoshi
Makishima, Tomoko
Lukashevich, Igor S.
Paessler, Slobodan
author_facet Reyna, Rachel A.
Maruyama, Junki
Mantlo, Emily K.
Manning, John T.
Taniguchi, Satoshi
Makishima, Tomoko
Lukashevich, Igor S.
Paessler, Slobodan
author_sort Reyna, Rachel A.
collection PubMed
description Lassa virus (LASV) is a zoonotic virus endemic to western Africa that can cause a potentially lethal and hemorrhagic disease, Lassa fever (LF). Survivors suffer a myriad of sequelae, most notably sudden onset sensorineural hearing loss (SNHL), the mechanism of which remains unclear. Unfortunately, studies aiming to identify the mechanism of these sequelae are limited due to the biosafety level 4 (BSL4) requirements of LASV itself. ML29, a reassortant virus proposed as an experimental vaccine candidate against LASV, is potentially an ideal surrogate model of LF in STAT1-/- mice due to similar phenotype in these animals. We intended to better characterize ML29 pathogenesis and potential sequelae in this animal model. Our results indicate that while both CD4 and CD8 T cells are responsible for acute disease in ML29 infection, ML29 induces significant hearing loss in a mechanism independent of either CD4 or CD8 T cells. We believe that this model could provide valuable information for viral-associated hearing loss in general.
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spelling pubmed-95985172022-10-27 Depletion of CD4 and CD8 T Cells Reduces Acute Disease and Is Not Associated with Hearing Loss in ML29-Infected STAT1-/- Mice Reyna, Rachel A. Maruyama, Junki Mantlo, Emily K. Manning, John T. Taniguchi, Satoshi Makishima, Tomoko Lukashevich, Igor S. Paessler, Slobodan Biomedicines Article Lassa virus (LASV) is a zoonotic virus endemic to western Africa that can cause a potentially lethal and hemorrhagic disease, Lassa fever (LF). Survivors suffer a myriad of sequelae, most notably sudden onset sensorineural hearing loss (SNHL), the mechanism of which remains unclear. Unfortunately, studies aiming to identify the mechanism of these sequelae are limited due to the biosafety level 4 (BSL4) requirements of LASV itself. ML29, a reassortant virus proposed as an experimental vaccine candidate against LASV, is potentially an ideal surrogate model of LF in STAT1-/- mice due to similar phenotype in these animals. We intended to better characterize ML29 pathogenesis and potential sequelae in this animal model. Our results indicate that while both CD4 and CD8 T cells are responsible for acute disease in ML29 infection, ML29 induces significant hearing loss in a mechanism independent of either CD4 or CD8 T cells. We believe that this model could provide valuable information for viral-associated hearing loss in general. MDPI 2022-09-29 /pmc/articles/PMC9598517/ /pubmed/36289695 http://dx.doi.org/10.3390/biomedicines10102433 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Reyna, Rachel A.
Maruyama, Junki
Mantlo, Emily K.
Manning, John T.
Taniguchi, Satoshi
Makishima, Tomoko
Lukashevich, Igor S.
Paessler, Slobodan
Depletion of CD4 and CD8 T Cells Reduces Acute Disease and Is Not Associated with Hearing Loss in ML29-Infected STAT1-/- Mice
title Depletion of CD4 and CD8 T Cells Reduces Acute Disease and Is Not Associated with Hearing Loss in ML29-Infected STAT1-/- Mice
title_full Depletion of CD4 and CD8 T Cells Reduces Acute Disease and Is Not Associated with Hearing Loss in ML29-Infected STAT1-/- Mice
title_fullStr Depletion of CD4 and CD8 T Cells Reduces Acute Disease and Is Not Associated with Hearing Loss in ML29-Infected STAT1-/- Mice
title_full_unstemmed Depletion of CD4 and CD8 T Cells Reduces Acute Disease and Is Not Associated with Hearing Loss in ML29-Infected STAT1-/- Mice
title_short Depletion of CD4 and CD8 T Cells Reduces Acute Disease and Is Not Associated with Hearing Loss in ML29-Infected STAT1-/- Mice
title_sort depletion of cd4 and cd8 t cells reduces acute disease and is not associated with hearing loss in ml29-infected stat1-/- mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598517/
https://www.ncbi.nlm.nih.gov/pubmed/36289695
http://dx.doi.org/10.3390/biomedicines10102433
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