ApoD mediates age- associated increase in vulnerability to influenza virus infection

• 成果类型: Article
• 署名作者: Jiang, Zhimin; Pan, Wenliang; Chen, Yu; Zhou, Dongliang; Ren, Shuning; Tong, Qi; Liu, Litao; Sun, Honglei; Sun, Yipeng; Bi, Yuhai; Wang, Dayan; Lu, Lu; Pu, Juan; Chang, Kin - Chow; Liu, Jinhua
• 署名单位: China Agricultural University; Chinese Academy of Sciences; Institute of Microbiology, CAS; Chinese Center for Disease Control & Prevention; National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control & Prevention; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; University of Nottingham
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8428
• DOI: 10.1073/pnas.2423973122
• 发表日期: 2025-09-16
• 关键词: mitochondria; disease

摘要

Influenza A virus (IAV) infection causes significantly greater morbidity and mortality in the elderly population, but the molecular mechanisms in the aging process responsible for severe infection remain unclear. In this study, we found that increased severity in IAV infection and reduced innate immune response correlated with extensive mitophagy in senescent human cells and in the lung of aged mice. Apolipoprotein D (ApoD) was identified as strongly elevated in the lungs and sera of aged human (>65 y old) and mouse (>21 mo old). ApoD was able to localize to mitochondria and interact, through its interferon response and promoted virus replication. ApoD deficiency, on the other hand, protected older mice from severe influenza and improved survival. Likewise, depletion and restored innate immune antiviral response, limiting virus propagation and associated promotes virus replication and infection severity, and is therefore a promising target for inhibition to improve disease outcome in older patients.