Persisting viruses and chronic inflammation: understanding their relation to autoimmunity

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Abstract
Viral infections may induce and sustain autoimmune processes via several and overlapping mechanisms. We outline how chronic inflammation, sustained by persisting viruses, may be "the prerequisite" for initiation and maintenance of the multistep process leading to autoimmunity. Chronic inflammation may favour priming of autoreactive T cells which have escaped thymic tolerance and are able to mount a cross-reactive response to self-mimicking antigens carried by viruses in the periphery. Moreover, chronic inflammation and persisting viruses can synergistically support autoimmunity through other relevant mechanisms: unveiling of cryptic self-epitopes, determinant spreading, activation of dendritic cells, constant priming of new autoreactive T cells, and efficient generation and restimulation of memory cells. Therefore, viruses seem to play a key role among the many environmental factors which, together with the genetic background, have been implicated in the pathogenesis of autoimmune diseases. We will also discuss some hypotheses explaining why autoimmunity is a rare event.