Virus-induced cellular senescence causes pulmonary sequelae post-influenza infection - 08/04/25

The Influenza A virus (IAV) infection dramatically raises rates of morbidity and mortality throughout the world. Our hypothesis is that respiratory viral infections can cause cellular senescence, which can hinder lung healing and lead to long-term lung impairments like emphysema and fibrosis.

To investigate whether IAV-induced cell senescence results in long-term lung damage in a mouse model, we employed pharmacological, genetic, and immunolabelling techniques.

Cellular senescence was observed in the bronchial epithelia of mice infected with a sublethal dose of IAV H₁N1p2009, beginning on day 4 post-infection (dpi) and progressing to the parenchyma on day 7. Even 28 days after infection, cellular senescence persisted; at 90 dpi, it started to decline. The lungs displayed senescence-related indicators, such as upregulated p16 and p21 and DNA damage expression triggered by gamma-H₂A. X. On day 28, the infection greatly altered the lungs’ structure and remodeling, resulting in fibrosis, abrasion of the airway epithelium, emphysema, and damage to the bronchi and alveoli, particularly in regions where senescent cell accumulation took place. Similar findings were found in nonhuman primates infected with IAV, where senescent cells within the bronchi survived due to insufficient repair of the airway epithelium. When rapalog AP20187 was used to deplete p16-expressing cells, lung fibrosis, emphysema, and inflammation were reduced in p16-ATTAC mice. Remarkably, the airway epithelium healed completely 28 days following the injury, demonstrating the rapidity with which the epithelial repair mechanism operates. Treatment with the senolytic drug ABT-263 also effectively increases epithelial repair, but emphysema and fibrosis did not change.

The virus-induced cellular senescence responsible for part of the influenza after effects in the lungs. Targeting senescent cells specifically could be advantageous in terms of therapy.