甲型 H7N9 流感病毒在老年非人灵长类动物中的发病机制。
Pathogenesis of Influenza A(H7N9) Virus in Aged Nonhuman Primates.
机构信息
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
出版信息
J Infect Dis. 2020 Sep 1;222(7):1155-1164. doi: 10.1093/infdis/jiaa267.
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.
摘要
甲型 H7N9 禽流感病毒导致人类死亡率高，尤其是老年人；然而，对于这种病毒的发病机制知之甚少。在目前的研究中，我们使用非人类灵长类动物来评估衰老对 A(H7N9)病毒致病性的影响。我们观察到，感染老龄动物（定义为 20-26 岁）的 A(H7N9)病毒比感染年轻动物（定义为 2-3 岁）引起的症状更严重。在老龄动物中，肺部炎症较弱，病毒感染持续存在。尽管大多数老龄动物肺部的细胞因子和趋化因子表达低于年轻动物肺部，但 1 只老龄动物表现出严重症状和失调的促炎细胞因子和趋化因子产生。这些结果表明，老龄动物免疫反应减弱或失调导致感染 A(H7N9)病毒的老年患者出现严重症状。
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