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

Abstract 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 exa...

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Autores principales:	Philippe Noriel Q. Pascua, Heba H. Mostafa, Bindumadhav M. Marathe, Peter Vogel, Charles J. Russell, Richard J. Webby, Elena A. Govorkova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7da29f5496134819a444fecc6c174e45
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spelling	oai:doaj.org-article:7da29f5496134819a444fecc6c174e452021-12-02T16:06:30ZPathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection10.1038/s41598-017-07433-z2045-2322https://doaj.org/article/7da29f5496134819a444fecc6c174e452017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07433-zhttps://doaj.org/toc/2045-2322Abstract 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.Philippe Noriel Q. PascuaHeba H. MostafaBindumadhav M. MarathePeter VogelCharles J. RussellRichard J. WebbyElena A. GovorkovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Philippe Noriel Q. Pascua Heba H. Mostafa Bindumadhav M. Marathe Peter Vogel Charles J. Russell Richard J. Webby Elena A. Govorkova Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection
description	Abstract 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.
format	article
author	Philippe Noriel Q. Pascua Heba H. Mostafa Bindumadhav M. Marathe Peter Vogel Charles J. Russell Richard J. Webby Elena A. Govorkova
author_facet	Philippe Noriel Q. Pascua Heba H. Mostafa Bindumadhav M. Marathe Peter Vogel Charles J. Russell Richard J. Webby Elena A. Govorkova
author_sort	Philippe Noriel Q. Pascua
title	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_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_sort	pathogenicity and peramivir efficacy in immunocompromised murine models of influenza b virus infection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7da29f5496134819a444fecc6c174e45
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Pathogenicity and peramivir efficacy in immunocompromised murine models of influenza B virus infection

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