Abstract
Infection with the Epstein-Barr virus (EBV) is associated with several malignancies and autoimmune diseases in humans. The following EBV infection and establishment of latency, recurrences frequently occur resulting in potential viral DNA shedding, which may then trigger the activation of immune pathways. We have previously demonstrated that levels of the pro-inflammatory cytokine IL-17, which is associated with several autoimmune diseases, are increased in response to EBV DNA injection in mice. Whether other pro-inflammatory pathways are induced in EBV DNA pathobiology remains to be investigated. The complexity of mammalian immune systems presents a challenge to studying differential activities of their intricate immune pathways in response to a particular immune stimulus. In this study, we used Drosophila melanogaster to identify innate humoral and cellular immune pathways that are activated in response to EBV DNA. Injection of wild-type adult flies with EBV DNA induced the immune deficiency (IMD) pathway resulting in enhanced expression of the antimicrobial peptide diptericin. Furthermore, EBV DNA increased the number of hemocytes in flies. Conditional silencing of the IMD pathway decreased diptericin expression in addition to curbing of hemocyte proliferation in response to challenge with EBV DNA. Comparatively, upon injecting mice with EBV DNA, we detected enhanced expression of tumor necrosis factor-α (TNFα); this enhancement is rather comparable to IMD pathway activation in flies. This study hence indicates that D. melanogaster could possibly be utilized to identify immune mediators that may also play a role in the response to EBV DNA in higher systems.
Highlights
The Epstein-Bar virus (EBV) is a human pathogen that belongs to the herpes family of viruses
Whereas we did not observe an increase in the expression of drosomycin (Figure 1) or the stress-inducible humoral factor Turandot (TotA) (Figure 2) upon Epstein-Barr virus (EBV) DNA treatment, we detected a 115-fold increase (p = 0.0002) in the transcriptional levels of diptericin (Figure 3) in the group injected with 70 copies of EBV DNA on day 1 post-injection
Worth noting is that an injection of 144 × 103 copies of EBV DNA in mice, which we had previously reported to induce a prominent elevation of IL-17A levels and demonstrated to induce tumor necrosis factor-α (TNFα) expression in mice, is equivalent to administration of 140 copies of EBV in flies; whereas this dose appears to be immunostimulatory in mice, a similar observation is not seen in flies
Summary
The Epstein-Bar virus (EBV) is a human pathogen that belongs to the herpes family of viruses. EBV DNA and Drosophila melanogaster disorders (PTLD) This virus is associated with multiple autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) (Lünemann et al, 2007; Draborg et al, 2013). A number of underlying mechanisms that link EBV to autoimmunity have been proposed; these have ranged from molecular mimicry to sequestered antigen release (reviewed in Ascherio and Munger, 2015). Despite these various proposed mechanisms, evidence that conclusively indicates one to mediate autoimmunity by EBV remains lacking; this likely indicates that multiple mechanisms are involved
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
