Cargando…

Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir

The main antivirals employed to combat seasonal and pandemic influenza are oseltamivir and zanamivir which act by inhibiting the virus-encoded neuraminidase. These have to be deployed close to the time of infection and antiviral resistance to the more widely used oseltamivir has arisen relatively ra...

Descripción completa

Detalles Bibliográficos
Autores principales: Dimmock, Nigel J., Dove, Brian K., Meng, Bo, Scott, Paul D., Taylor, Irene, Cheung, Linda, Hallis, Bassam, Marriott, Anthony C., Carroll, Miles W., Easton, Andrew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526778/
https://www.ncbi.nlm.nih.gov/pubmed/23041142
http://dx.doi.org/10.1016/j.antiviral.2012.09.017
_version_ 1782253620977205248
author Dimmock, Nigel J.
Dove, Brian K.
Meng, Bo
Scott, Paul D.
Taylor, Irene
Cheung, Linda
Hallis, Bassam
Marriott, Anthony C.
Carroll, Miles W.
Easton, Andrew J.
author_facet Dimmock, Nigel J.
Dove, Brian K.
Meng, Bo
Scott, Paul D.
Taylor, Irene
Cheung, Linda
Hallis, Bassam
Marriott, Anthony C.
Carroll, Miles W.
Easton, Andrew J.
author_sort Dimmock, Nigel J.
collection PubMed
description The main antivirals employed to combat seasonal and pandemic influenza are oseltamivir and zanamivir which act by inhibiting the virus-encoded neuraminidase. These have to be deployed close to the time of infection and antiviral resistance to the more widely used oseltamivir has arisen relatively rapidly. Defective interfering (DI) influenza virus is a natural antiviral that works in a different way to oseltamivir and zanamivir, and a cloned version (segment 1 244 DI RNA in a cloned A/PR/8/34 virus; 244/PR8) has proved effective in preclinical studies in mice. The active principle is the DI RNA, and this is thought to interact with all influenza A viruses by inhibiting RNA virus synthesis and packaging of the cognate virion RNA into nascent DI virus particles. We have compared the ability of DI virus and oseltamivir to protect ferrets from intranasal 2009 pandemic influenza virus A/California/04/09 (A/Cal, H1N1). Ferrets were treated with a single 2 μg intranasal dose of 244 DI RNA delivered as 244/PR8 virus, or a total of 25 mg/kg body weight of oseltamivir given as 10 oral doses over 5 days. Both DI virus and oseltamivir reduced day 2 infectivity and the influx of cells into nasal fluids, and permitted the development of adaptive immunity. However DI virus, but not oseltamivir, significantly reduced weight loss, facilitated better weight gain, reduced respiratory disease, and reduced infectivity on days 4 and 6. 244 DI RNA was amplified by A/Cal by >25,000-fold, consistent with the amelioration of clinical disease. Treatment with DI virus did not delay clearance or cause persistence of infectious virus or DI RNA. Thus in this system DI virus was overall more effective than oseltamivir in combatting pandemic A/California/04/09.
format Online
Article
Text
id pubmed-3526778
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-35267782012-12-24 Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir Dimmock, Nigel J. Dove, Brian K. Meng, Bo Scott, Paul D. Taylor, Irene Cheung, Linda Hallis, Bassam Marriott, Anthony C. Carroll, Miles W. Easton, Andrew J. Antiviral Res Article The main antivirals employed to combat seasonal and pandemic influenza are oseltamivir and zanamivir which act by inhibiting the virus-encoded neuraminidase. These have to be deployed close to the time of infection and antiviral resistance to the more widely used oseltamivir has arisen relatively rapidly. Defective interfering (DI) influenza virus is a natural antiviral that works in a different way to oseltamivir and zanamivir, and a cloned version (segment 1 244 DI RNA in a cloned A/PR/8/34 virus; 244/PR8) has proved effective in preclinical studies in mice. The active principle is the DI RNA, and this is thought to interact with all influenza A viruses by inhibiting RNA virus synthesis and packaging of the cognate virion RNA into nascent DI virus particles. We have compared the ability of DI virus and oseltamivir to protect ferrets from intranasal 2009 pandemic influenza virus A/California/04/09 (A/Cal, H1N1). Ferrets were treated with a single 2 μg intranasal dose of 244 DI RNA delivered as 244/PR8 virus, or a total of 25 mg/kg body weight of oseltamivir given as 10 oral doses over 5 days. Both DI virus and oseltamivir reduced day 2 infectivity and the influx of cells into nasal fluids, and permitted the development of adaptive immunity. However DI virus, but not oseltamivir, significantly reduced weight loss, facilitated better weight gain, reduced respiratory disease, and reduced infectivity on days 4 and 6. 244 DI RNA was amplified by A/Cal by >25,000-fold, consistent with the amelioration of clinical disease. Treatment with DI virus did not delay clearance or cause persistence of infectious virus or DI RNA. Thus in this system DI virus was overall more effective than oseltamivir in combatting pandemic A/California/04/09. Elsevier 2012-12 /pmc/articles/PMC3526778/ /pubmed/23041142 http://dx.doi.org/10.1016/j.antiviral.2012.09.017 Text en © 2012 Elsevier B.V. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Dimmock, Nigel J.
Dove, Brian K.
Meng, Bo
Scott, Paul D.
Taylor, Irene
Cheung, Linda
Hallis, Bassam
Marriott, Anthony C.
Carroll, Miles W.
Easton, Andrew J.
Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir
title Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir
title_full Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir
title_fullStr Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir
title_full_unstemmed Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir
title_short Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir
title_sort comparison of the protection of ferrets against pandemic 2009 influenza a virus (h1n1) by 244 di influenza virus and oseltamivir
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526778/
https://www.ncbi.nlm.nih.gov/pubmed/23041142
http://dx.doi.org/10.1016/j.antiviral.2012.09.017
work_keys_str_mv AT dimmocknigelj comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir
AT dovebriank comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir
AT mengbo comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir
AT scottpauld comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir
AT taylorirene comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir
AT cheunglinda comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir
AT hallisbassam comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir
AT marriottanthonyc comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir
AT carrollmilesw comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir
AT eastonandrewj comparisonoftheprotectionofferretsagainstpandemic2009influenzaavirush1n1by244diinfluenzavirusandoseltamivir