Mimotope-hormesis and mortalin/grp75/mthsp70: a new hypothesis on how infectious disease-associated epitope mimicry may explain low cancer burden in developing nations.
It is generally observed that countries with heavy infectious burden show lower cancer incidence as compared to more affluent nations. With the emerging paradigm on microbial heat shock proteins (hsps) as molecular link between infections and autoimmune diseases, we posit a new hypothesis, the "mimotope-hormesis", on the immunologic impact of infections on regional cancer prevention. According to this, assaults of infection during early adulthood could fortify the immune system to evoke more potent defenses against late-onset diseases, such as cancer, via autoimmunity. Interestingly, both experimental and clinical data support the beneficial role of autoimmunity in long-term cancer survivors. We illustrate this by a comprehensive in silico mimotope (epitope mimicry) analysis of human infectious pathogens against mortalin (mthsp70/PB74/GRP75), a type of hsp70 protein involved in control of cell proliferation, immortalization and tumorigenesis.
Deocaris
Custer C
CC
Cell Proliferation Research Team, Gene Function Research Center, National Institute of Advanced Industrial Science & Technology (AIST), 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan.
Taira
Kazunari
K
Kaul
Sunil C
SC
Wadhwa
Renu
R
D003141:Communicable Diseases / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology*; D003906:Developing Countries; D000939:Epitopes / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D024101:Mitochondrial Proteins; D018716:Molecular Mimicry; D009369:Neoplasms / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology*
D000939:Epitopes; D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C018551:glucose-regulated proteins; C080352:mortalin