Tirofiban protects mice against severe RSV pneumonia by potentially inhibiting platelet activation via the GPIbα–vWF pathway

This study aimed to investigate the role of platelets in mediating lethal respiratory syncytial virus (RSV) infection and to explore the potential of antiplatelet therapy as a novel therapeutic approach for RSV infection. Ex vivo and in vivo experiments were used to study the effects of lethal RSV infection on platelet activation, aggregation, and thrombus formation. The emerging therapeutic effect of tirofiban, a GPIIb/IIIa inhibitor, in mitigating RSV-induced pneumonia was also evaluated. Mice infected with a highly virulent RSV strain (R96-5) developed severe RSV pneumonia and showed significantly increased mortality rates, along with extensive platelet infiltration and thrombus formation in the lungs. In situ hybridization revealed co-localization of RSV nucleocapsid RNA with the platelet GPIbα gene in lung tissue. RSV infection induced marked platelet aggregation through the GPIbα-vWF pathway. Notably, tirofiban significantly protected mice from severe pneumonia caused by R96-5. These findings highlight the critical involvement of platelet activation and aggregation in RSV infection and suggest that targeting platelet through the GPIbα–vWF signaling axis may represent a promising therapeutic strategy for severe RSV infection.