Abstract
Enteroviruses, especially group B coxsackieviruses (CV-B), have been associated with the development of chronic diseases such as type 1 diabetes (T1D). The pathological mechanisms that trigger virus-induced autoimmunity against islet antigens in T1D are not fully elucidated. Animal and human studies suggest that NK cells response to CV-B infection play a crucial role in the enteroviral pathogenesis of T1D. Indeed, CV-B-infected cells can escape from cytotoxic T cells recognition and destruction by inhibition of cell surface expression of HLA class I antigen through non-structural viral proteins, but they can nevertheless be killed by NK cells. Cytolytic activity of NK cells towards pancreatic beta cells persistently-infected with CV-B has been reported and defective viral clearance by NK cells of patients with T1D has been suggested as a mechanism leading to persistence of CV-B and triggering autoimmunity reported in these patients. The knowledge about host antiviral defense against CV-B infection is not only crucial to understand the susceptibility to virus-induced T1D but could also contribute to the design of new preventive or therapeutic approaches for individuals at risk for T1D or newly diagnosed patients.
Highlights
Type 1 diabetes (T1D) is a chronic autoimmune disease that results from the selective destruction and loss of functional insulin-producing pancreatic islet beta cells occurring in genetically predisposed individuals and probably triggered or accelerated by environmental factors such as drugs, toxins, nutrients and viruses [1,2,3,4]
Flodström et al observed in transgenic NOD mice expressing the suppressor of cytokine signaling-1 (SOCS-1) that coxsackievirus-B4 infection can induce an acute form of autoimmune diabetes including early and severe hyperglycemia and insulitis with loss of insulin beta cells [115]
We found that CV-B4 can establish a persistent infection in human pancreatic beta cells up to several months with low levels of viral replication [31]
Summary
Type 1 diabetes (T1D) is a chronic autoimmune disease that results from the selective destruction and loss of functional insulin-producing pancreatic islet beta cells occurring in genetically predisposed individuals and probably triggered or accelerated by environmental factors such as drugs, toxins, nutrients and viruses [1,2,3,4]. Even though most enteroviral infections remain asymptomatic, they have been associated with a wide spectrum of clinical signs ranging from relatively mild symptoms such as fever, gastro-enteritis, skin lesions and headache to severe acute forms such as meningitis, hepatitis, encephalitis, myocarditis, pancreatitis and hand, foot and mouth disease [10,12,13,14,15] In addition to these severe acute clinical features, enteroviral infections, especially infections with coxsackievirus B (CV-B) (Human enterovirus B), are the most suspected environmental factors involved in the development of chronic diseases such as T1D [4,5,6,16]; the precise etiology and the mechanisms that trigger virus-induced autoimmunity against islet antigens are not fully understood. The issue of the role of NK cells response to CV-B infection in the pathogenesis of T1D is addressed
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