Epigenetic Changes Mediated by MicroRNA miR29 Activate Cyclooxygenase 2 and Lambda-1 Interferon Production during Viral Infection

• DOI: 10.1128/jvi.06169-11
• Publication Date: 2011-11-10T01:42:06Z
• Authors: Jiali Fang; Qian Hao; Li Liu; Yongkui Li; Jianguo Wu; Xixiang Huo; Ying Zhu
• Keywords: Viral infection

Lambda-1 interferon (IFN-λ1) and cyclooxygenase-2 (COX-2) were reported to play an important role in host antiviral defense. However, the mechanism by which IFN-λ1 COX2 are activated modulated during viral infection remains unclear. In this study, we found that expression of both circulating COX2-derived prostaglandin E2 (PGE2) was coordinately elevated a cohort influenza patients compared healthy individuals. Expression blocked selective inhibitor A virus A549 human lung epithelial cells but enhanced overexpression COX2, indicating production is dependent. able increase promoting NF-κB binding enhancer promoter. We epigenetic changes activate PGE2 accumulation infection. The DNA methyltransferase 3a (DNMT3a) DNMT3b, not DNMT1, downregulated following peripheral blood mononuclear (PBMCs). showed microRNA miR29 suppresses DNMT activity thus induces PGE2. Furthermore, 50-fold virally infected 10-fold PBMCs from patients, after mock or individuals, respectively. Activation protein kinase signaling pathway phosphorylation CREB1 also contributed expression. Collectively, our work defines novel proinflammatory cascade control