Epstein-Barr Virus andHuman herpes virus 6Type A DNA Enhance IL-17 Production in Mice

Abstract

Several studies have shown a potential association between the Herpesviridae members, the Epstein-Barr virus (EBV) and Human herpes virus 6 (HHV-6), and an increased risk of autoimmune disease development. Because of the ability of these viruses to cause recurrent infections, various viral antigens, including viral DNA, are consistently shed. These antigens may then play a role in triggering autoimmune processes or contributing to autoimmune mechanisms. Therefore, this study examined whether the DNA of EBV or that of HHV-6A is capable of triggering IL-17, the autoimmune-associated cytokine, in mice. BALB/c mice were intraperitoneally injected with various copy numbers of either EBV or HHV-6A DNA. One group was injected with sterile water (the DNA solvent), and another was left uninjected. A mouse group that was administered DNA obtained from Staphylococcus epidermidis was included to ensure that any observed effects would pertain to the viral DNA tested. Mice were sacrificed and their sera were examined using an enzyme-linked immunosorbent assay for IL-17 and IL-23, as pro-autoimmune cytokines, IL-10, as an anti-inflammatory cytokine, and IFN-γ, as a pro-inflammatory cytokine, on days 3, 6, and 9 post-injection. All mouse groups injected with different copy numbers of EBV DNA or HHV-6A DNA displayed higher IL-17 levels than did the group injected with water on days 3, 6, and 9 post-injection. The highest IL-17 levels appeared to coincide with a marked increase in IL-23 and a decrease in IL-10 levels. Unlike the S. epidermidis DNA, which increased IFN-γ levels but not IL-17 or IL-23 levels, the viral DNA tested increased all three mediators, indicating that triggering Th17 responses is a specific property of EBV and HHV-6A DNA. In conclusion, EBV and HHV-6A viral DNA are capable of enhancing the production of the pro-inflammatory cytokine IL-17, which has been shown to play a role in autoimmune diseases.

Yin and yang of interleukin-17 in host immunity to infection

“…In contrast, IL-17 is associated with the pathology in 2009 pandemic influenza A (H1N1)-induced acute lung injury 140 . Additionally, IL-17 levels are associated with the exacerbated disease pathology induced following viral infections such as hepatitis 141, 142 , vaccinia virus 143, 144 , RSV 145– 147 , HSV 148, 149 , and EBV 150, 151 . During viral infections (such as hepatitis), IL-17 can either potentiate early neutrophil infiltration at the site of infection 152 or inhibit NK cell-mediated host immune response (for example, vaccinia virus infection) 153 .…”

Porphyromonas endodontalis reactivates latent Epstein–Barr virus

“…, Rahal et al . ); thus, EBV may be associated with not only carcinogenesis but also pathogenesis in local inflammation.…”

“…EBV has also been implicated in malignancies such as gastric cancer, Hodgkin disease and T-cell lymphoma (Abe et al 2015, Chua et al 2015, Vockerodt et al 2015. EBV infection induces expression of proinflammatory cytokines such as tumour necrosis factor-a, interleukin (IL)-1b, IL-8, IL-10, IL-12, and IL-17 (Morris et al 2008, Murakami et al 2014, Rahal et al 2015; thus, EBV may be associated with not only carcinogenesis but also pathogenesis in local inflammation.…”

Endosomal Toll-Like Receptors Mediate Enhancement of Interleukin-17A Production Triggered by Epstein-Barr Virus DNA in Mice

“…In a previous study, we reported that EBV DNA enhances the production of the proinflammatory cytokine IL-17A as well as IL-23, tumor necrosis factor (TNF-␣), and IFN-␥ when injected into mice (25,65). IL-17A plays a role in host defenses against bacterial and fungal infections (26).…”