Rhinovirus Infection May Contribute to Esophageal Inflammation in Eosinophilic Esophagitis

Abstract Eosinophil esophagitis (EoE) shares many epidemiologic and pathophysiologic characteristics with other allergic diseases, especially allergic asthma. Since rhinovirus (RV) infection is known to contribute to inflammation in allergic asthma, we sought to investigate whether RV might also contribute to esophageal inflammation in EoE through epithelial activation. In vitro cultures of primary esophageal epithelial cells and a human non-transformed immortalized esophageal epithelial cell line (EPC2-hTERT) grown submerged or at air-liquid interface (ALI) were infected with RV-A1a or RV-A16. In addition, we added Interleukin (IL)-13 to mimic EoE conditions. RV-binding receptors, RV replication, and interferon lambda-1 (IFNL1) response to infection were measured. RNA-Sequencing (RNA-Seq) on RV-infected EPC2-hTERT cultures was performed for gene ontology analysis and compared to published RNA-Seq data of esophageal biopsies from EoE patients. Both RV receptors were expressed by esophageal cells. After infection, we observed higher RV viral gene expression, indicative of active replication. IL-13 had little effect on replication in monolayers but was required in ALI for replication to occur. IFNL1 mRNA was induced by RV-A1a in both cell types and IFNL1 protein was increased in IL-13-treated EPC2-hTERT monolayers. Gene ontology analysis of our in vitro experimental model highlighted virus-induced processes and increased interferon activity. In addition, we found overlapping genes between our RNA-Seq results of EPC2-hTERT cells and publicly available RNA-Seq data from esophageal biopsies of patients with EoE versus healthy control donors. Our data suggest the possibility that viruses such as RV may contribute to esophageal inflammation and play an important role in the inception and/or persistence of EoE.