The Impact of -Associated Junction Plakoglobin on Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants, young children, and immunocompromised individuals. Currently, FDA-approved monoclonal antibody therapies are limited to infants and young children with severe RSV disease. As a result, there is an urgent need for comprehensive studies of RSV pathogenesis to support the development of new therapeutic strategies. Exchange proteins directly activated by cAMP () have recently emerged as key regulators in various viral infections. Our previous work identified EPAC isoform 2 () as a critical factor in RSV replication and host innate immune responses. However, the molecular mechanisms underlying 's role in RSV infection remain unclear. In this study, we investigated -mediated RSV infection by identifying -interacting proteins. Proteomics and immunoprecipitation analyses revealed that junction plakoglobin () interacts with in both mock- and RSV-infected cells, with this interaction notably enhanced during RSV infection. To determine 's role in RSV infection, we compared viral replication in -deficient and control cells. downregulation significantly reduced the production of infectious RSV particles, likely by impairing viral budding and viral gene transcription. Moreover, our findings indicate that is essential for an effective cellular immune response to RSV infection. Together, these results suggest that and may cooperatively regulate RSV replication and dissemination.