C96-09 How RSV Triggers Lung Inflammation and Potential New Treatments

Abstract Respiratory syncytial virus (RSV) is a common virus that causes severe lung infections, especially in babies, older adults, and people with weak immune systems. Although there are two FDA-approved RSV vaccines for the elderly aged 60 years and older, there is no FDA-approved and cost-effective RSV treatment available for treating infants and young children who are suffering from RSV-driven bronchiolitis, and many cases are admitted to hospitals. Our research shows that RSV uses a cellular structure called the ARP2/3 complex, which helps control cell shape and movement, to cause harmful inflammation in the lungs. This process, which we call cytoskeletal inflammation, worsens the infection. We studied this by growing human lung cells in two ways: a 3D model (using primary normal human bronchial epithelial cells in air-liquid interface cultures) and a 2D model (using A549 cells). We infected these cells with the RSV A2 strain and observed changes over 3 to 6 days. We found that RSV activates key parts of the ARP2/3 complex—ARP2, N-WASP, and CDC42—which help the virus spread and form thread-like structures called filopodia. This activation also caused the lung cell layers to thicken, similar to the airway swelling seen in RSV-related illnesses like bronchiolitis. We’re now testing drugs that block the ARP2/3 complex to see if they can reduce the virus’s spread and calm the inflammation, helping to keep the airways healthy. This work points to the ARP2/3 complex as a promising target for new RSV treatments, offering hope for better ways to fight this virus. This abstract is funded by: NIH & UND