Scientists identify age-linked protein that weakens immunity against influenza virus

Researchers have discovered that high levels of the protein apolipoprotein D (ApoD) in the lungs of older people impair antiviral defences, making influenza infections more severe, highlighting ApoD as a promising therapeutic target

Scientists have discovered why older people are more likely to experience severe illness from influenza and have identified a potential target to reduce this risk.

In their research the investigators found that older people produced much higher levels of apolipoprotein D (ApoD), a glycosylated protein involved in lipid metabolism and inflammation, than younger individuals. Elevated levels of ApoD reduced the body’s ability to resist viral infection and resulted in more serious disease outcomes.

The team established that excess ApoD production in the lungs during ageing caused extensive tissue damage and impaired the protective antiviral type I interferon response. They concluded that ApoD acted as an age-related cellular factor that diminished immune defence against influenza virus infection by triggering extensive mitochondrial mitophagy. This damage would then increase viral replication and exacerbate lung injury. Mitochondria are essential both for cellular energy production and for the induction of protective interferons.

The research was an international collaboration led by scientists from China Agricultural University, the Institute of Microbiology at the Chinese Academy of Sciences, the National Institute for Viral Disease Control and Prevention at the Chinese Centre for Disease Control and Prevention, all of Beijing China, and the universities of Nottingham and Edinburgh, in the United Kingdom.

“Aging is a leading risk factor in influenza-related deaths. Furthermore, the global population is aging at an unprecedented rate in human history, posing major issues for healthcare and the economy.

So, we need to find out why older patients often suffer more severely from influenza virus infection,” said Professor Kin-Chow Chang from the School of Veterinary Medicine and Science at the University of Nottingham, and co-author of the paper.

The study used a mouse model where the subjects were older, alongside donor human tissue sections to investigate why influenza severity increases with age. Identification of ApoD as a key factor has provided a rationale to explore therapeutic strategies.

ApoD is now regarded as a promising target for medical intervention to protect older individuals against severe influenza virus infection. Such an approach could reduce both morbidity and mortality in ageing populations.

“There is now an exciting opportunity to therapeutically ameliorate disease severity of the elderly from influenza virus infection by the inhibitory targeting of ApoD,” said Professor Chang.

For further reading please visit: 10.1073/pnas.2423973122