IAV Induced IL-35 Expression And The Antiviral Function Of IL-35

The novel IL-35 was a secreted protein which composed of EBI3 and p35. IL-35 has been reported as a pro inflammatory cytokine with inhibitory function, and related with inflammatory diseases, autoimmune diseases and cell apoptosis. However, little is known about the relationship between IL-35 and virus infection. Here we did preliminary research on IAV induced IL-35 expression and the biological function of IL-35 in response to viral infectioaPart 1 introduced the update researches of IL-35 and reviewed the IL-12 family, influenza A virus and interferons.Part 2 is the main research content of this article, describes IAV upregulated IL-35 expression, and the role of IL-35 during viral infection.First, we show that the high expression of IL-35 in the blood and throat swab samples of IAV patients. Then, we found IAV induced IL-35 production in A549, PBMC and AT-Ⅱ cells. Next we investigated that IL-35 was upregulated by IAV via NF-κB/p65 transcription binding site and through COX-2 and iNOS pathways. Interestingly, IL-35 acted anti-viral function to DNA virus like HBV and RNA virus as IAV, EV71 and VSV. IL-35 induced type Ⅰ and type Ⅲ IFN and the downstream factor including PKR, OAS and Mx to inhibit viral infection.Our results suggested that IAV induced IL-35 expression through COX-2 and iNOS pathways and enhancing by NF-κB/p65.Meanwhile, IL-35 played broad-spectrum anti-viral activity. Our study provided theoretical basis for development IL-35 as the potential candidates of anti-viral drugs.