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

Author:

Fukuyama Satoshi1,Iwatsuki-Horimoto Kiyoko1,Kiso Maki1,Nakajima Noriko2,Gregg Robert W3,Katsura Hiroaki1,Tomita Yuriko1,Maemura Tadashi145,da Silva Lopes Tiago Jose14,Watanabe Tokiko1,Shoemaker Jason E136,Hasegawa Hideki7,Yamayoshi Seiya1ORCID,Kawaoka Yoshihiro15

Affiliation:

1. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

2. Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan

3. Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

4. Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, Wisconsin, USA

5. Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 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

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.

Funder

Strategic Basic Research Programs from the Japan Science and Technology Agency

Japan Initiative for Global Research Network on Infectious Diseases

Japan Agency for Medical Research and Development

Ministry of Education, Culture, Science, Sports, and Technology of Japan

National Institute of Allergy and Infectious Diseases

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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