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

doi:10.3390/v13020345

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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

^1,†

^2,†

¹,

¹,

³,

Willy M. J. M. Bogers

and

Gerrit Koopman

^1,*

Department of Virology, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ Rijswijk, The Netherlands

Department of Parasitology, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ Rijswijk, The Netherlands

Animal Science Department, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ Rijswijk, The Netherlands

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editors: Karol Sestak and Mahesh Mohan

Viruses 2021, 13(2), 345; https://doi.org/10.3390/v13020345

Received: 8 January 2021 / Revised: 10 February 2021 / Accepted: 18 February 2021 / Published: 22 February 2021

(This article belongs to the Special Issue Non-human Primate Models of Viral and Autoimmune Diseases)

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Abstract

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. View Full-Text

Keywords: influenza; H5N1; infection; aerosol; macaques

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MDPI and ACS Style

Mooij, P.; Stammes, M.A.; Mortier, D.; Fagrouch, Z.; van Driel, N.; Verschoor, E.J.; Kondova, I.; Bogers, W.M.J.M.; Koopman, G. Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques. Viruses 2021, 13, 345. https://doi.org/10.3390/v13020345

AMA Style

Mooij P, Stammes MA, Mortier D, Fagrouch Z, van Driel N, Verschoor EJ, Kondova I, Bogers WMJM, Koopman G. Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques. Viruses. 2021; 13(2):345. https://doi.org/10.3390/v13020345

Chicago/Turabian Style

Mooij, Petra, Marieke A. Stammes, Daniella Mortier, Zahra Fagrouch, Nikki van Driel, Ernst J. Verschoor, Ivanela Kondova, Willy M. J. M. Bogers, and Gerrit Koopman. 2021. "Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques" Viruses 13, no. 2: 345. https://doi.org/10.3390/v13020345

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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

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