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-Giovanny Peniche-Trujillo, 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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