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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Bibliographic Details
Published in:The Journal of infectious diseases 2020-09, Vol.222 (7), p.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: Article
Language:English
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
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Summary: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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiaa267