Chapter 5 : Antigenic Mimicry between Self and Coxsackievirus Proteins Leads to Both Humoral and Cellular Autoimmunity to Heart Proteins

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Antigenic Mimicry between Self and Coxsackievirus Proteins Leads to Both Humoral and Cellular Autoimmunity to Heart Proteins, Page 1 of 2

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Enteroviruses have evolved mechanisms for terminal shutoff of host protein synthesis. These mechanisms involve viral protease 2A degradation of the cellular p220 protein cap-dependent binding complex or degradation of poly(A)-binding protein. These mechanisms are not operative in all infected cells that replicate these viruses to the usual titers of 100 to 2,500 virions per cell. Indeed, many types of cells, including cardiac fibroblasts, that are permissive for replication of coxsackievirus group B (CVB) strains exhibit little to no viral cytopathic effects during production of virus for days to weeks. Three major mechanisms probably cause cardiac dysfunction in patients with viral myocarditis and dilated cardiomyopathy (DCM). These include: injury directly due to virus infection and replication in the heart, damage mediated by specific and nonspecific host defense responses to the infection, and autoimmunity to cardiac antigens triggered by virus infection. A conundrum exists between poor cardiac function in patients with severe chronic myocarditis or DCM and the often minimal pathologic alterations found in their heart tissues upon autopsy. Antigenic mimicry at the T-cell level has been demonstrated between heart antigens and various pathogens, including group A streptococci, , chlamydia, cytomegalovirus, and CVB. Adoptive transfer of lymphocytes from ANT-reactive patients also transferred myocarditis into severe combined immunodeficient mice. Finally, murine T cells from CVB3-infected mice respond to adenine nucleotide translocator (ANT), again indicating not only that different pathogens may share the same epitope but also that a single pathogen is likely to have multiple distinct mimicking epitopes with diverse heart proteins.

Citation: Huber S, Gauntt C. 2000. Antigenic Mimicry between Self and Coxsackievirus Proteins Leads to Both Humoral and Cellular Autoimmunity to Heart Proteins, p 57-68. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch5

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