Spike proteins of coronaviruses activate mast cells for degranulation via stimulating Src/PI3K/AKT/Ca ²⁺ intracellular signaling cascade

The activation and degranulation of mast cells (MCs), triggered by a variety of viruses, are intricately linked to viral pathogenesis. However, the precise mechanism underlying virus-induced MC degranulation remains largely unknown. In this study, we demonstrate the ubiquity of coronavirus-induced MC degranulation and investigate the intracellular signaling pathways that mediate this process. We reveal that the binding of Spike proteins and cellular receptors is sufficient to elicit MC activation for rapid degranulation. This binding triggers the activation of src kinase and the downstream PI3K/AKT cellular signaling pathway, resulting in an accumulation of intracellular calcium ions. These calcium ions subsequently facilitate microtubule-dependent granule transport, ultimately promoting MC degranulation. This study elucidates the mechanism underlying virus-triggered activation of MCs and has the potential to aid in the development of MC-targeted antiviral therapeutic strategies.