Viruses and autoimmunity

Kim, Bumseok; Kaistha, Shilpa Deshpande; Rouse, Barry T.

doi:10.1080/08916930500484708

Cited by 41 publications

(29 citation statements)

References 57 publications

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“…Autoimmunity characterized by the generation of autoAbs and the activation of autoreactive lymphocytes has been demonstrated in a number of viral infections, such as human immunodeficiency virus, hepatitis C virus, cytomegalovirus, herpes simplex virus and Epstein-Barr virus [26][27][28][29][30][31][32] . The generation of autoAbs cross-reactive with endothelial cells is involved in several autoimmune vascular diseases [33][34][35] .…”

Section: Discussionmentioning

confidence: 99%

C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry

Wan¹,

Lin²,

Chen³

et al. 2008

American J. of Infectious Diseases

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Infection with dengue virus (DV) causes diseases ranging from self-limited dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, thrombocytopenia and bleeding are the clinical manifestations associated with dengue hemorrhage. We previously showed that anti-DV nonstructural protein 1 (NS1) antibodies (Abs) cross-reacted with endothelial cells. The potential target proteins on endothelial cell surface recognized by anti-DV NS1 Abs showed sequence homology with the C-terminal amino acids (a.a.) 311-352 of DV NS1. In this study, the role of NS1 C-terminal region in dengue autoimmunity was investigated. We deleted the a.a. 277-352 of DV NS1 to prepare truncated NS1 (tNS1) and generated anti-DV tNS1 Abs in mice. The endothelial cell-binding activity of anti-DV tNS1 Abs was lower than that of anti-DV NS1 Abs. In addition, the endothelial cell-binding activity of anti-DV NS1 Abs was inhibited by preabsorption with DV NS1 but not with DV tNS1 proteins. The anti-P311 (a.a. 311-330) and anti-P331 (a.a. 331-350) titers of dengue patient sera were positively correlated with their endothelial cell-binding activity. Dengue patient sera showed lower binding activity to DV tNS1 than to DV NS1 proteins. The endothelial cell-binding activity of dengue patient sera was inhibited by preabsorption with P311 and P331. This study helps to understand the molecular mechanisms of autoimmunity mediated by anti-DV NS1 Abs and to provide the potential implications of tNS1 in dengue vaccine strategies.

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Section: Discussionmentioning

confidence: 99%

C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry

Wan¹,

Lin²,

Chen³

et al. 2008

American J. of Infectious Diseases

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“…Thus, there are instances when molecular mimicry may account for the development of autoimmunity in the eye. In contrast, the immunosuppressive environment of the eye appears to limit the potential for bystander activation 28 , although such activation cannot be ruled out 29 .…”

Section: Introductionmentioning

confidence: 98%

Ocular antigen does not cause disease unless presented in the context of inflammation

Voigt

Wikström

Kezic

et al. 2017

Sci Rep

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Ocular antigens are sequestered behind the blood-retina barrier and the ocular environment protects ocular tissues from autoimmune attack. The signals required to activate autoreactive T cells and allow them to cause disease in the eye remain in part unclear. In particular, the consequences of peripheral presentation of ocular antigens are not fully understood. We examined peripheral expression and presentation of ocular neo-self-antigen in transgenic mice expressing hen egg lysozyme (HEL) under a retina-specific promoter. High levels of HEL were expressed in the eye compared to low expression throughout the lymphoid system. Adoptively transferred naïve HEL-specific CD4+ T cells proliferated in the eye draining lymph nodes, but did not induce uveitis. By contrast, systemic infection with a murine cytomegalovirus (MCMV) engineered to express HEL induced extensive proliferation of transferred naïve CD4+ T cells, and significant uveoretinitis. In this model, wild-type MCMV, lacking HEL, did not induce overt uveitis, suggesting that disease is mediated by antigen-specific peripherally activated CD4+ T cells that infiltrate the retina. Our results demonstrate that retinal antigen is presented to T cells in the periphery under physiological conditions. However, when the same antigen is presented during viral infection, antigen-specific T cells access the retina and autoimmune uveitis ensues.

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“…MS is perceived as a disease of autoimmunity against antigens of the central nervous system (Greer and McCombe 2011). This framework, the autoimmune hypothesis, revolves around mechanisms of the immune system, such as the autoreactivity of T cells to CNS antigens, linkage of immune-relevant genes to MS patients, and the influence of Vitamin D on immune response (Challoner et al 1995;Kim et al 2006;McCoy et al 2006;Ascherio and Munger 2007;Broadley 2007;Cantorna 2008;Fensterl and Sen 2009;Ramagopalan et al 2009;Ascherio et al 2010;Beretich and Beretich 2010;Grant 2010;Lünemann et al 2010;Greer and McCombe 2011).…”

Section: Introductionmentioning

confidence: 99%

Multiple Sclerosis is Not a Disease of the Immune System

Corthals¹

2011

The Quarterly Review of Biology

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Multiple sclerosis is a complex neurodegenerative disease, thought to arise through autoimmunity against antigens of the central nervous system. The autoimmunity hypothesis fails to explain why genetic and environmental risk factors linked to the disease in one population tend to be unimportant in other populations. Despite great advances in documenting the cell and molecular mechanisms underlying MS pathophysiology, the autoimmunity framework has also been unable to develop a comprehensive explanation of the etiology of the disease. I propose a new framework for understanding MS as a dysfunction of the metabolism of lipids. Specifically, the homeostasis of lipid metabolism collapses during acute-phase inflammatory response triggered by a pathogen, trauma, or stress, starting a feedback loop of increased oxidative stress, inflammatory response, and proliferation of cytoxic foam cells that cross the blood brain barrier and both catabolize myelin and prevent remyelination. Understanding MS as a chronic metabolic disorder illuminates four aspects of disease onset and progression: 1) its pathophysiology; 2) genetic susceptibility; 3) environmental and pathogen triggers; and 4) the skewed sex ratio of patients. It also suggests new avenues for treatment.

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Viruses and autoimmunity

Cited by 41 publications

References 57 publications

C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry

C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry

Ocular antigen does not cause disease unless presented in the context of inflammation

Multiple Sclerosis is Not a Disease of the Immune System

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