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How Herpesviridae Combined with other Viral Infections can Trigger and Drive Rheumatoid Arthritis

Marina I. Arleevskaya, Olga A. Kravtsova, Anatoly P. Tsibulkin, Julie Lemerle and Yves Renaudineau

Rheumatoid arthritis (RA) development results from an inadequate immune response to environmental challenges in genetically predisposed patients. The list of viruses associated with RA is still growing, and includes the cytomegalovirus, the Epstein-Barr virus, and the herpes simplex viruses. Several hypotheses support their causative role. Firstly, RA development may result from a polyviral community or the cumulative effect of several microbial/viral factors thus explaining the absence of a single defined pathogen. Secondly, the process of RA development from preclinical to late-stage disease may result from cumulative episodes of viral infections caused by distinct pathogens. Thirdly, viral agents may trigger RA when associated with other factors such as tobacco, ethnic differences, psychological stress, inflammation, or chronic joint tissue micro-trauma. On the other hand, others consider that RA development occurs even with ordinary infection frequency and duration and results from immune hypersensitivity to viral infections which can lead to loss of tolerance to self-antigens.