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Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques

Infection with highly pathogenic avian H5N1 influenza virus in humans often leads to severe respiratory disease with high mortality. Experimental infection in non-human primates can provide additional insight into disease pathogenesis. However, such a model should recapitulate the disease symptoms o...

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Autores principales: Mooij, Petra, Stammes, Marieke A., Mortier, Daniella, Fagrouch, Zahra, van Driel, Nikki, Verschoor, Ernst J., Kondova, Ivanela, Bogers, Willy M. J. M., Koopman, Gerrit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926951/
https://www.ncbi.nlm.nih.gov/pubmed/33671829
http://dx.doi.org/10.3390/v13020345
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author Mooij, Petra
Stammes, Marieke A.
Mortier, Daniella
Fagrouch, Zahra
van Driel, Nikki
Verschoor, Ernst J.
Kondova, Ivanela
Bogers, Willy M. J. M.
Koopman, Gerrit
author_facet Mooij, Petra
Stammes, Marieke A.
Mortier, Daniella
Fagrouch, Zahra
van Driel, Nikki
Verschoor, Ernst J.
Kondova, Ivanela
Bogers, Willy M. J. M.
Koopman, Gerrit
author_sort Mooij, Petra
collection PubMed
description Infection with highly pathogenic avian H5N1 influenza virus in humans often leads to severe respiratory disease with high mortality. Experimental infection in non-human primates can provide additional insight into disease pathogenesis. However, such a model should recapitulate the disease symptoms observed in humans, such as pneumonia and inflammatory cytokine response. While previous studies in macaques have demonstrated the occurrence of typical lesions in the lungs early after infection and a high level of immune activation, progression to severe disease and lethality were rarely observed. Here, we evaluated a routinely used combined route of infection via intra-bronchial, oral, and intra-nasal virus inoculation with aerosolized H5N1 exposure, with or without the regular collection of bronchoalveolar lavages early after infection. Both combined route and aerosol exposure resulted in similar levels of virus replication in nose and throat and similar levels of immune activation, cytokine, and chemokine release in the blood. However, while animals exposed to H5N1 by combined-route inoculation developed severe disease with high lethality, aerosolized exposure resulted in less lesions, as measured by consecutive computed tomography and less fever and lethal disease. In conclusion, not virus levels or immune activation, but route of infection determines fatal outcome for highly pathogenic avian H5N1 influenza infection.
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spelling pubmed-79269512021-03-04 Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques Mooij, Petra Stammes, Marieke A. Mortier, Daniella Fagrouch, Zahra van Driel, Nikki Verschoor, Ernst J. Kondova, Ivanela Bogers, Willy M. J. M. Koopman, Gerrit Viruses Article Infection with highly pathogenic avian H5N1 influenza virus in humans often leads to severe respiratory disease with high mortality. Experimental infection in non-human primates can provide additional insight into disease pathogenesis. However, such a model should recapitulate the disease symptoms observed in humans, such as pneumonia and inflammatory cytokine response. While previous studies in macaques have demonstrated the occurrence of typical lesions in the lungs early after infection and a high level of immune activation, progression to severe disease and lethality were rarely observed. Here, we evaluated a routinely used combined route of infection via intra-bronchial, oral, and intra-nasal virus inoculation with aerosolized H5N1 exposure, with or without the regular collection of bronchoalveolar lavages early after infection. Both combined route and aerosol exposure resulted in similar levels of virus replication in nose and throat and similar levels of immune activation, cytokine, and chemokine release in the blood. However, while animals exposed to H5N1 by combined-route inoculation developed severe disease with high lethality, aerosolized exposure resulted in less lesions, as measured by consecutive computed tomography and less fever and lethal disease. In conclusion, not virus levels or immune activation, but route of infection determines fatal outcome for highly pathogenic avian H5N1 influenza infection. MDPI 2021-02-22 /pmc/articles/PMC7926951/ /pubmed/33671829 http://dx.doi.org/10.3390/v13020345 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mooij, Petra
Stammes, Marieke A.
Mortier, Daniella
Fagrouch, Zahra
van Driel, Nikki
Verschoor, Ernst J.
Kondova, Ivanela
Bogers, Willy M. J. M.
Koopman, Gerrit
Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques
title Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques
title_full Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques
title_fullStr Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques
title_full_unstemmed Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques
title_short Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques
title_sort aerosolized exposure to h5n1 influenza virus causes less severe disease than infection via combined intrabronchial, oral, and nasal inoculation in cynomolgus macaques
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926951/
https://www.ncbi.nlm.nih.gov/pubmed/33671829
http://dx.doi.org/10.3390/v13020345
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