Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape

ABSTRACT The 1918 influenza virus, subtype H1N1, was the causative agent of the most devastating pandemic in the history of infectious diseases. In vitro studies have confirmed that extreme virulence is an inherent property of this virus. Here, we utilized the macaque model for evaluating the effica...

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Autores principales:	Friederike Feldmann, Darwyn Kobasa, Carissa Embury-Hyatt, Allen Grolla, Tracy Taylor, Maki Kiso, Satoshi Kakugawa, Jason Gren, Steven M. Jones, Yoshihiro Kawaoka, Heinz Feldmann
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	1918 influenza virus treatment oseltamivir drug resistance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/082069db9c264c958063094bd9099c59
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spelling	oai:doaj.org-article:082069db9c264c958063094bd9099c592021-11-15T15:59:41ZOseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape10.1128/mBio.02059-192150-7511https://doaj.org/article/082069db9c264c958063094bd9099c592019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02059-19https://doaj.org/toc/2150-7511ABSTRACT The 1918 influenza virus, subtype H1N1, was the causative agent of the most devastating pandemic in the history of infectious diseases. In vitro studies have confirmed that extreme virulence is an inherent property of this virus. Here, we utilized the macaque model for evaluating the efficacy of oseltamivir phosphate against the fully reconstructed 1918 influenza virus in a highly susceptible and relevant disease model. Our findings demonstrate that oseltamivir phosphate is effective in preventing severe disease in macaques but vulnerable to virus escape through emergence of resistant mutants, especially if given in a treatment regimen. Nevertheless, we conclude that oseltamivir would be highly beneficial to reduce the morbidity and mortality rates caused by a highly pathogenic influenza virus although it would be predicted that resistance would likely emerge with sustained use of the drug. IMPORTANCE Oseltamivir phosphate is used as a first line of defense in the event of an influenza pandemic prior to vaccine administration. Treatment failure through selection and replication of drug-resistant viruses is a known complication in the field and was also demonstrated in our study with spread of resistant 1918 influenza virus in multiple respiratory tissues. This emphasizes the importance of early treatment and the possibility that noncompliance may exacerbate treatment effectiveness. It also demonstrates the importance of implementing combination therapy and vaccination strategies as soon as possible in a pandemic situation.Friederike FeldmannDarwyn KobasaCarissa Embury-HyattAllen GrollaTracy TaylorMaki KisoSatoshi KakugawaJason GrenSteven M. JonesYoshihiro KawaokaHeinz FeldmannAmerican Society for Microbiologyarticle1918 influenza virustreatmentoseltamivirdrug resistanceMicrobiologyQR1-502ENmBio, Vol 10, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	1918 influenza virus treatment oseltamivir drug resistance Microbiology QR1-502
spellingShingle	1918 influenza virus treatment oseltamivir drug resistance Microbiology QR1-502 Friederike Feldmann Darwyn Kobasa Carissa Embury-Hyatt Allen Grolla Tracy Taylor Maki Kiso Satoshi Kakugawa Jason Gren Steven M. Jones Yoshihiro Kawaoka Heinz Feldmann Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape
description	ABSTRACT The 1918 influenza virus, subtype H1N1, was the causative agent of the most devastating pandemic in the history of infectious diseases. In vitro studies have confirmed that extreme virulence is an inherent property of this virus. Here, we utilized the macaque model for evaluating the efficacy of oseltamivir phosphate against the fully reconstructed 1918 influenza virus in a highly susceptible and relevant disease model. Our findings demonstrate that oseltamivir phosphate is effective in preventing severe disease in macaques but vulnerable to virus escape through emergence of resistant mutants, especially if given in a treatment regimen. Nevertheless, we conclude that oseltamivir would be highly beneficial to reduce the morbidity and mortality rates caused by a highly pathogenic influenza virus although it would be predicted that resistance would likely emerge with sustained use of the drug. IMPORTANCE Oseltamivir phosphate is used as a first line of defense in the event of an influenza pandemic prior to vaccine administration. Treatment failure through selection and replication of drug-resistant viruses is a known complication in the field and was also demonstrated in our study with spread of resistant 1918 influenza virus in multiple respiratory tissues. This emphasizes the importance of early treatment and the possibility that noncompliance may exacerbate treatment effectiveness. It also demonstrates the importance of implementing combination therapy and vaccination strategies as soon as possible in a pandemic situation.
format	article
author	Friederike Feldmann Darwyn Kobasa Carissa Embury-Hyatt Allen Grolla Tracy Taylor Maki Kiso Satoshi Kakugawa Jason Gren Steven M. Jones Yoshihiro Kawaoka Heinz Feldmann
author_facet	Friederike Feldmann Darwyn Kobasa Carissa Embury-Hyatt Allen Grolla Tracy Taylor Maki Kiso Satoshi Kakugawa Jason Gren Steven M. Jones Yoshihiro Kawaoka Heinz Feldmann
author_sort	Friederike Feldmann
title	Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape
title_short	Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape
title_full	Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape
title_fullStr	Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape
title_full_unstemmed	Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape
title_sort	oseltamivir is effective against 1918 influenza virus infection of macaques but vulnerable to escape
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/082069db9c264c958063094bd9099c59
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Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape

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