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Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection

Influenza B viruses are important human pathogens that remain inadequately studied, largely because available animal models are poorly defined. Here, we developed an immunocompromised murine models for influenza B virus infection, which we subsequently used to study pathogenicity and to examine anti...

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Autores principales: Pascua, Philippe Noriel Q., Mostafa, Heba H., Marathe, Bindumadhav M., Vogel, Peter, Russell, Charles J., Webby, Richard J., Govorkova, Elena A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544712/
https://www.ncbi.nlm.nih.gov/pubmed/28779075
http://dx.doi.org/10.1038/s41598-017-07433-z
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author Pascua, Philippe Noriel Q.
Mostafa, Heba H.
Marathe, Bindumadhav M.
Vogel, Peter
Russell, Charles J.
Webby, Richard J.
Govorkova, Elena A.
author_facet Pascua, Philippe Noriel Q.
Mostafa, Heba H.
Marathe, Bindumadhav M.
Vogel, Peter
Russell, Charles J.
Webby, Richard J.
Govorkova, Elena A.
author_sort Pascua, Philippe Noriel Q.
collection PubMed
description Influenza B viruses are important human pathogens that remain inadequately studied, largely because available animal models are poorly defined. Here, we developed an immunocompromised murine models for influenza B virus infection, which we subsequently used to study pathogenicity and to examine antiviral efficacy of the neuraminidase inhibitor peramivir. We studied three influenza B viruses that represent both the Yamagata (B/Massachusetts/2/2012 and B/Phuket/3073/2013) and Victoria (B/Brisbane/60/2008, BR/08) lineages. BR/08 was the most pathogenic in genetically modified immunocompromised mice [BALB scid and non-obese diabetic (NOD) scid strains] causing lethal infection without prior adaptation. The immunocompromised mice demonstrated prolonged virus shedding with modest induction of immune responses compared to BALB/c. Rather than severe virus burden, BR/08 virus-associated disease severity correlated with extensive virus spread and severe pulmonary pathology, stronger and persistent natural killer cell responses, and the extended induction of pro-inflammatory cytokines and chemokines. In contrast to a single-dose treatment (75 mg/kg/day), repeated doses of peramivir rescued BALB scid mice from lethal challenge with BR/08, but did not result in complete virus clearance. In summary, we have established immunocompromised murine models for influenza B virus infection that will facilitate evaluations of the efficacy of currently available and investigational anti-influenza drugs.
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spelling pubmed-55447122017-08-07 Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection Pascua, Philippe Noriel Q. Mostafa, Heba H. Marathe, Bindumadhav M. Vogel, Peter Russell, Charles J. Webby, Richard J. Govorkova, Elena A. Sci Rep Article Influenza B viruses are important human pathogens that remain inadequately studied, largely because available animal models are poorly defined. Here, we developed an immunocompromised murine models for influenza B virus infection, which we subsequently used to study pathogenicity and to examine antiviral efficacy of the neuraminidase inhibitor peramivir. We studied three influenza B viruses that represent both the Yamagata (B/Massachusetts/2/2012 and B/Phuket/3073/2013) and Victoria (B/Brisbane/60/2008, BR/08) lineages. BR/08 was the most pathogenic in genetically modified immunocompromised mice [BALB scid and non-obese diabetic (NOD) scid strains] causing lethal infection without prior adaptation. The immunocompromised mice demonstrated prolonged virus shedding with modest induction of immune responses compared to BALB/c. Rather than severe virus burden, BR/08 virus-associated disease severity correlated with extensive virus spread and severe pulmonary pathology, stronger and persistent natural killer cell responses, and the extended induction of pro-inflammatory cytokines and chemokines. In contrast to a single-dose treatment (75 mg/kg/day), repeated doses of peramivir rescued BALB scid mice from lethal challenge with BR/08, but did not result in complete virus clearance. In summary, we have established immunocompromised murine models for influenza B virus infection that will facilitate evaluations of the efficacy of currently available and investigational anti-influenza drugs. Nature Publishing Group UK 2017-08-04 /pmc/articles/PMC5544712/ /pubmed/28779075 http://dx.doi.org/10.1038/s41598-017-07433-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pascua, Philippe Noriel Q.
Mostafa, Heba H.
Marathe, Bindumadhav M.
Vogel, Peter
Russell, Charles J.
Webby, Richard J.
Govorkova, Elena A.
Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection
title Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection
title_full Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection
title_fullStr Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection
title_full_unstemmed Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection
title_short Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection
title_sort pathogenicity and peramivir efficacy in immunocompromised murine models of influenza b virus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544712/
https://www.ncbi.nlm.nih.gov/pubmed/28779075
http://dx.doi.org/10.1038/s41598-017-07433-z
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