Pathogenesis of Influenza A(H7N9) Virus in Aged Nonhuman Primates

Abstract The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In the current study, we used nonhuman primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We ob...

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Published inThe Journal of infectious diseases Vol. 222; no. 7; pp. 1155 - 1164
Main Authors Fukuyama, Satoshi, Iwatsuki-Horimoto, Kiyoko, Kiso, Maki, Nakajima, Noriko, Gregg, Robert W, Katsura, Hiroaki, Tomita, Yuriko, Maemura, Tadashi, da Silva Lopes, Tiago Jose, Watanabe, Tokiko, Shoemaker, Jason E, Hasegawa, Hideki, Yamayoshi, Seiya, Kawaoka, Yoshihiro
Format Journal Article
LanguageEnglish
Published US Oxford University Press 01.09.2020
Subjects
Aging
Animals
Avian flu
Chemokines
Cytokines
Cytokines - immunology
Disease Models, Animal
Female
Geriatrics
Immune response
Infections
Inflammation
Influenza
Influenza A
Influenza A Virus, H7N9 Subtype
Lung - immunology
Lung - pathology
Lung - virology
Lungs
Macaca fascicularis
Major and Brief Reports
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - virology
Pathogenicity
Virus Replication
influenza
Aging
nonhuman primate
dysregulated immunity
immune senescence
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Abstract Abstract The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In the current study, we used nonhuman primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as age 20–26 years) caused more severe symptoms than infection of young animals (defined as age 2–3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, 1 aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus. Aged cynomolgus macaques experienced greater symptom severity than younger animals after A(H7N9) virus infection because of immune senescence or dysregulated immune responses.
AbstractList The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In the current study, we used nonhuman primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as age 20–26 years) caused more severe symptoms than infection of young animals (defined as age 2–3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, 1 aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus.
The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In the current study, we used nonhuman primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as age 20-26 years) caused more severe symptoms than infection of young animals (defined as age 2-3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, 1 aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus.The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In the current study, we used nonhuman primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as age 20-26 years) caused more severe symptoms than infection of young animals (defined as age 2-3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, 1 aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus.
The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In the current study, we used nonhuman primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as age 20–26 years) caused more severe symptoms than infection of young animals (defined as age 2–3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, 1 aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus. Aged cynomolgus macaques experienced greater symptom severity than younger animals after A(H7N9) virus infection because of immune senescence or dysregulated immune responses.
Abstract The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In the current study, we used nonhuman primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as age 20–26 years) caused more severe symptoms than infection of young animals (defined as age 2–3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, 1 aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus. Aged cynomolgus macaques experienced greater symptom severity than younger animals after A(H7N9) virus infection because of immune senescence or dysregulated immune responses.
Author da Silva Lopes, Tiago Jose
Iwatsuki-Horimoto, Kiyoko
Gregg, Robert W
Watanabe, Tokiko
Yamayoshi, Seiya
Kiso, Maki
Fukuyama, Satoshi
Nakajima, Noriko
Tomita, Yuriko
Kawaoka, Yoshihiro
Shoemaker, Jason E
Katsura, Hiroaki
Maemura, Tadashi
Hasegawa, Hideki
AuthorAffiliation 2 Department of Pathology, National Institute of Infectious Diseases , Tokyo, Japan
6 Department of Computational and Systems Biology, University of Pittsburgh , Pittsburgh, Pennsylvania, USA
7 Influenza Virus Research Center, National Institute of Infectious Diseases , Tokyo, Japan
5 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo , Tokyo, Japan
1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo , Tokyo, Japan
4 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin–Madison , Madison, Wisconsin, USA
3 Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania, USA
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ContentType Journal Article
Copyright The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2020
The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Copyright_xml – notice: The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2020
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Keywords influenza
Aging
nonhuman primate
dysregulated immunity
immune senescence
Language English
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Snippet Abstract The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic...
The avian influenza A(H7N9) virus has caused high mortality rates in humans, especially in the elderly; however, little is known about the mechanistic basis...
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SubjectTerms Aging
Animals
Avian flu
Chemokines
Cytokines
Cytokines - immunology
Disease Models, Animal
Female
Geriatrics
Immune response
Infections
Inflammation
Influenza
Influenza A
Influenza A Virus, H7N9 Subtype
Lung - immunology
Lung - pathology
Lung - virology
Lungs
Macaca fascicularis
Major and Brief Reports
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - virology
Pathogenicity
Virus Replication
Title Pathogenesis of Influenza A(H7N9) Virus in Aged Nonhuman Primates
URI https://www.ncbi.nlm.nih.gov/pubmed/32433769
https://www.proquest.com/docview/2473811764
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https://pubmed.ncbi.nlm.nih.gov/PMC7459135
Volume 222
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