Chapter 40 : Viruses, Autoimmunity, and Cancer

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Viruses, Autoimmunity, and Cancer, Page 1 of 2

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The autoimmune disorder multiple sclerosis (MS) is an instructive example in which several pieces of evidence suggest that a microbial infection is the trigger for disease, with most evidence pointing to viral infections. Initial trigger of an autoimmune response could occur through several mechanisms, including molecular mimicry, bystander activation, epitope spreading, or super-antigen activation. In 1964, Epstein-Barr virus (EBV) was demonstrated to be caused by virus infection by electron microscopy in cells cultured from Burkitt's lymphoma, but it was not until the early 1980s that the causal relationship between other viruses and cancer was acknowledged. Human papillomaviruses (HPV) can be used a model to illustrate how a virus can induce cancer. The molecular pathogenesis of cancer caused by the high-risk HPV types is not fully understood and, although they are self-sufficient to induce carcinogenesis, the infection itself is not able to induce the malignant transformation of infected cells. For a very long time, polyomaviruses (PyV) have been proposed to have a causal link with cancer, because under experimental conditions, cells which are nonpermissive for viral replication can be transformed by PyVs. Over the past decades, more and more viruses have been causally linked to different forms of human and animal cancer. Today, one cancer case in five is caused by an infectious agent. With techniques developing rapidly, more associations between viruses and malignancies can be expected in the coming years.

Citation: Getts M, Bogaert L, Kast W, Miller S. 2011. Viruses, Autoimmunity, and Cancer, p 511-520. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch40
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Mechanisms of infection-induced autoimmunity. Circulating T cells are generally specific for some pathogen-derived or otherwise foreign antigen (virus antigen recognized by a virus-specific T cell, in the example here); however, some circulating T cells also possess a capacity for recognizing self-tissues (autoreactive T cell). A virus infection (for example) could elicit autoimmunity through several mechanisms. Molecular mimicry (A) occurs when T cells are cross-reactive with self and viral antigens, so that a viral infection can activate a T cell that is capable of recognizing a self-antigen as foreign. Bystander activation (B) occurs when tissue damage results in the release of self-antigens that are recognized by autoreactive cells. Such tissue damage could occur due to inflammatory mediators, including cytokines that are released by infected cells and other cells detecting the presence of a pathogen through PAMPs. By extension, epitope spreading can occur when the autoreactive response spreads to other self-antigens, exacerbating the autoimmune process. Superantigen-induced activation of autoreactive cells (C) could occur if autoreactive cells are present within the population of T cells that are nonspecifically activated by a superantigen.

Citation: Getts M, Bogaert L, Kast W, Miller S. 2011. Viruses, Autoimmunity, and Cancer, p 511-520. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch40
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Selected murine models of infection-induced autoimmune diseases

Citation: Getts M, Bogaert L, Kast W, Miller S. 2011. Viruses, Autoimmunity, and Cancer, p 511-520. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch40
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Selected autoimmune diseases and their proposed viral associations and potential mechanisms

Citation: Getts M, Bogaert L, Kast W, Miller S. 2011. Viruses, Autoimmunity, and Cancer, p 511-520. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch40
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Criteria for defining a causal role for an infection in cancer

Citation: Getts M, Bogaert L, Kast W, Miller S. 2011. Viruses, Autoimmunity, and Cancer, p 511-520. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch40

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