Chapter 13 - The chaperone system in autoimmunity, inflammation, and virus-induced diseases: Role of chaperonins

Abstract

Stress caused by diverse stressors, e.g., virus infection, affects multiple cells and tissues and demands action of antistress mechanisms, e.g., the chaperone system (CS). Its chief components are the molecular chaperones, which are cytoprotective but, if abnormal in structure, function, location, and/or concentration, may cause diseases, the chaperonopathies. Pathogenic viruses need human CS to go through all the steps of their life cycles. Thus, the CS may be pathogenic directly or through viruses, as illustrated here by two members of the CS, the chaperonins Hsp60 and CCT (Chaperonin-Containing TCP-1). Hsp60 can cause inflammation and autoimmune disorders by inducing cells to produce proinflammatory cytokines or because it shares immunogenic-antigenic epitopes with invading pathogens like bacteria and viruses that elicit cross-reactive immune cells and antibodies. CCT is crucial for the life cycle of pathogenic viruses, acting in collaboration with other CS components. Thus, virus-caused pathologies are indirectly caused by the CS. Therapeutic strategies may include suppression of the genes encoding the pathogenic chaperone or blocking/inhibiting the genes' protein products. This negative chaperonotherapy offers hopes to treat chaperonopathies and virus-caused diseases, but the road to success can be predicted to be difficult because of the extreme molecular and functional complexities of the CS.