Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783659580635480064 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7926951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT mooijpetra aerosolizedexposuretoh5n1influenzaviruscauseslessseverediseasethaninfectionviacombinedintrabronchialoralandnasalinoculationincynomolgusmacaques AT stammesmariekea aerosolizedexposuretoh5n1influenzaviruscauseslessseverediseasethaninfectionviacombinedintrabronchialoralandnasalinoculationincynomolgusmacaques AT mortierdaniella aerosolizedexposuretoh5n1influenzaviruscauseslessseverediseasethaninfectionviacombinedintrabronchialoralandnasalinoculationincynomolgusmacaques AT fagrouchzahra aerosolizedexposuretoh5n1influenzaviruscauseslessseverediseasethaninfectionviacombinedintrabronchialoralandnasalinoculationincynomolgusmacaques AT vandrielnikki aerosolizedexposuretoh5n1influenzaviruscauseslessseverediseasethaninfectionviacombinedintrabronchialoralandnasalinoculationincynomolgusmacaques AT verschoorernstj aerosolizedexposuretoh5n1influenzaviruscauseslessseverediseasethaninfectionviacombinedintrabronchialoralandnasalinoculationincynomolgusmacaques AT kondovaivanela aerosolizedexposuretoh5n1influenzaviruscauseslessseverediseasethaninfectionviacombinedintrabronchialoralandnasalinoculationincynomolgusmacaques AT bogerswillymjm aerosolizedexposuretoh5n1influenzaviruscauseslessseverediseasethaninfectionviacombinedintrabronchialoralandnasalinoculationincynomolgusmacaques AT koopmangerrit aerosolizedexposuretoh5n1influenzaviruscauseslessseverediseasethaninfectionviacombinedintrabronchialoralandnasalinoculationincynomolgusmacaques |