Language
English
Publication Date
4-26-2025
Journal
Viruses
DOI
10.3390/v17050627
PMID
40431638
PMCID
PMC12115799
PubMedCentral® Posted Date
4-26-2025
PubMedCentral® Full Text Version
Post-print
Abstract
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 (EPAC) have recently emerged as key regulators in various viral infections. Our previous work identified EPAC isoform 2 (EPAC2) as a critical factor in RSV replication and host innate immune responses. However, the molecular mechanisms underlying EPAC2’s role in RSV infection remain unclear. In this study, we investigated EPAC2-mediated RSV infection by identifying EPAC2-interacting proteins. Proteomics and immunoprecipitation analyses revealed that junction plakoglobin (JUP) interacts with EPAC2 in both mock- and RSV-infected cells, with this interaction notably enhanced during RSV infection. To determine JUP’s role in RSV infection, we compared viral replication in JUP-deficient and control cells. JUP downregulation significantly reduced the production of infectious RSV particles, likely by impairing viral budding and viral gene transcription. Moreover, our findings indicate that JUP is essential for an effective cellular immune response to RSV infection. Together, these results suggest that EPAC2 and JUP may cooperatively regulate RSV replication and dissemination.
Keywords
Humans, Guanine Nucleotide Exchange Factors, Respiratory Syncytial Virus Infections, Virus Replication, Respiratory Syncytial Virus, Human, Cell Line, Host-Pathogen Interactions, EPAC2, JUP, RSV, viral gene transcription and viral genome replication
Published Open-Access
yes
Recommended Citation
Takle, Chaitra A; Choi, Eun-Jin; Choi, Eun Seok; et al., "The Impact of EPAC2-Associated Junction Plakoglobin on Respiratory Syncytial Virus Infection" (2025). Faculty and Staff Publications. 3843.
https://digitalcommons.library.tmc.edu/baylor_docs/3843