Exchange Protein Directly Activated by cAMP 2 Enhances Respiratory Syncytial Virus-Induced Pulmonary Disease in Mice

Junping Ren, Wenzhe Wu, Ke Zhang, Eun Jin Choi, Pingyuan Wang, Teodora Ivanciuc, Alex Peniche, Youwen Qian, Roberto P. Garofalo, Jia Zhou, Xiaoyong Bao

Research output: Contribution to journalArticlepeer-review

Abstract

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children. It is also a significant contributor to upper respiratory tract infections, therefore, a major cause for visits to the pediatrician. High morbidity and mortality are associated with high-risk populations including premature infants, the elderly, and the immunocompromised. However, no effective and specific treatment is available. Recently, we discovered that an exchange protein directly activated by cyclic AMP 2 (EPAC2) can serve as a potential therapeutic target for RSV. In both lower and upper epithelial cells, EPAC2 promotes RSV replication and pro-inflammatory cytokine/chemokine induction. However, the overall role of EPAC2 in the pulmonary responses to RSV has not been investigated. Herein, we found that EPAC2-deficient mice (KO) or mice treated with an EPAC2-specific inhibitor showed a significant decrease in body weight loss, airway hyperresponsiveness, and pulmonary inflammation, compared with wild-type (WT) or vehicle-treated mice. Overall, this study demonstrates the critical contribution of the EPAC2-mediated pathway to airway diseases in experimental RSV infection, suggesting the possibility to target EPAC2 as a promising treatment modality for RSV.

Original languageEnglish (US)
Article number757758
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Oct 18 2021

Keywords

  • EPAC2
  • RSV
  • immune response
  • inflammation
  • pulmonary disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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