Abstract

ObjectiveWe recently demonstrated that EBV DNA is correlated with proinflammatory responses in mice and in rheumatoid arthritis (RA) patients; hence, we utilized an RA mouse model to examine whether EBV DNA enhances the risk and severity of arthritis and to assess its immunomodulatory effects.MethodsC57BL/6J mice were treated with collagen (arthritis-inducing agent), EBV DNA 6 days before collagen, EBV DNA 15 days after collagen, Staphylococcus epidermidis DNA 6 days before collagen, EBV DNA alone, or water. Mice were then monitored for clinical signs and affected joints/footpads were histologically analysed. The relative concentration of IgG anti- chicken collagen antibodies and serum cytokine levels of IL-17A and IFNϒ were determined by ELISA. The number of cells co-expressing IL-17A and IFNϒ in joint histological sections was determined by immunofluorescence.ResultsThe incidence of arthritis was significantly higher in mice that received EBV DNA prior to collagen compared to mice that only received collagen. Similarly, increased clinical scores, histological scores and paw thicknesses with a decreased gripping strength were observed in groups treated with EBV DNA and collagen. The relative concentration of IgG anti-chicken collagen antibodies was significantly increased in the group that received EBV DNA 6 days prior to collagen in comparison to the collagen receiving group. On the other hand, the highest number of cells co-expressing IFNϒ and IL-17A was observed in joints from mice that received both collagen and EBV DNA.ConclusionEBV DNA increases the incidence and severity of arthritis in a RA mouse model. Targeting mediators triggered by viral DNA may hence be a potential therapeutic avenue.

Highlights

  • Epstein-Barr virus (EBV) belongs to the Herpesviridae family and is considered one of the most prevalent viruses that affect humans [1, 2]

  • The collageninduced arthritis (CIA) murine model in C57BL/6J mice was used to assess the effect of EBV DNA on the development of arthritis

  • Several studies have indicated that the incidence of arthritis in this model ranges between 50% and 80% [33, 39, 40]

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Summary

Introduction

Epstein-Barr virus (EBV) belongs to the Herpesviridae family and is considered one of the most prevalent viruses that affect humans [1, 2]. EBV establishes latency in B lymphocytes, which permits subsequent reactivation and recurrent infection. During these frequent recurrences EBV antigens including its DNA are shed [3]. EBV infection can be asymptomatic or may result in mild illness. If the infection is acquired during adolescence, it results in Infectious Mononucleosis (IM) [4]. EBV has been associated with malignant lymphoproliferative diseases such as Burkitt’s lymphoma, epithelial carcinomas such as nasopharyngeal carcinoma, and Human Immunodeficiency virus (HIV)-related diseases such as hairy leukoplakia [5]. EBV has been linked with an increased risk of developing autoimmune diseases such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) [6]

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