Mumps virus infects Beta cells in human fetal islet cell cultures upregulating the expression of HLA class I molecules

Parkkonen, Päivi; Hyöty, Heikki; Koskinen, Leena; Leinikki, Pauli

doi:10.1007/bf00400853

Cited by 50 publications

(23 citation statements)

References 37 publications

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“…In contrast, interferon-a (IFN-a)-a cytokine that is only induced during virus infections-has been found in b cells in diabetic patients, suggesting that a virus may be present in b cells [Huang et al, 1995]. Enteroviruses can also infect b cells in culture and can induce the expression of IFN-a and HLA molecules in b cells [Parkkonen et al, 1992;Roivainen et al, 2000;Chehadeh et al, 2000a].…”

Section: Discussionmentioning

confidence: 86%

Enterovirus infections are associated with the induction of β‐cell autoimmunity in a prospective birth cohort study

Salminen

Sadeharju

Lönnrot

et al. 2002

Journal of Medical Virology

130

135

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Enterovirus infections have been associated with the manifestation of clinical type 1 diabetes in a number of reports, and recent prospective studies have suggested that enterovirus infections may initiate the autoimmune process, leading to the disease. In the present study, we analyzed the role of enterovirus infections in a Finnish birth cohort study, Diabetes Prediction and Prevention (DIPP), in which all newborn infants are screened for diabetes-associated HLA-DQB1 alleles, and those with an increased genetic risk are invited for prospective follow-up. Enterovirus infections were diagnosed by serology and reverse transcriptase-polymerase chain reaction (RT-PCR) from serum samples taken from birth every 3-6 months. Case children included 41 infants who became positive for diabetes-associated autoantibodies during the observation. Control children comprised altogether 196 infants who remained autoantibody negative and were matched for the time of birth, sex, and HLA-DQB1 alleles. Enterovirus infections were more frequent in case children than in control children (P = 0.004), and the average enterovirus antibody levels were also higher in the case children (P = 0.003). Enterovirus infections were particularly frequent during the 6-month period preceding the first detection of autoantibodies: 51% of the case children compared with 28% of the control children had an infection in that time interval (P = 0.003). There was no difference in the frequency of adenovirus infections between the groups (P = 0.9). The present results imply that enterovirus infections are associated with the appearance of beta-cell autoantibodies. A possible causal relationship is supported by the clustering of infections to the time when autoantibodies appeared.

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Section: Discussionmentioning

confidence: 86%

Enterovirus infections are associated with the induction of β‐cell autoimmunity in a prospective birth cohort study

Salminen

Sadeharju

Lönnrot

et al. 2002

Journal of Medical Virology

130

135

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“…The excess of CD 8-positive T cells in infiltrated islets and increased expression of molecules recognized by these cells, i.e., HLA class I molecules, on islet cells further suggests that one important mechanism by which beta cells are destroyed, is direct action of cytotoxic T cells. Given their function in destroying target cells infected by viral pathogens (41) and given the detected increase in expression of HLA class I molecules on beta cells after virus infection (42), it is interesting to speculate on possible involvement ofa virus also in triggering the autoimmune process leading to beta cell destruction, although in this case of IDDM no evidence of an association between a virus and the disease process was obtained.…”

Section: Discussionmentioning

confidence: 96%

Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.

Hänninen

Jalkanen²,

Salmi³

et al. 1992

J. Clin. Invest.

216

117

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Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme-or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. Vft

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“…This might indicate ongoing virus-induced interferon secretion in the islets. We have previously shown that enterovirus infection in human pancreatic islets leads to such class I HLA hyperexpression in vitro partly mediated by secretion of type 1 interferons (23).…”

Section: Discussionmentioning

confidence: 99%

Detection of a Low-Grade Enteroviral Infection in the Islets of Langerhans of Living Patients Newly Diagnosed With Type 1 Diabetes

et al. 2014

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The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3–9 weeks after onset of type 1 diabetes in six adult patients (age 24–35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh-frozen whole pancreatic tissue using PCR and sequencing. Nondiabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetic patients (two of nine controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (one of nine controls). Enterovirus-specific RNA sequences were detected in four of six patients (zero of six controls). The results were confirmed in various laboratories. Only 1.7% of the islets contained VP1+ cells, and the amount of enterovirus RNA was low. The results provide evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, which is consistent with the possibility that a low-grade enteroviral infection in the pancreatic islets contributes to disease progression in humans.

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Mumps virus infects Beta cells in human fetal islet cell cultures upregulating the expression of HLA class I molecules

Cited by 50 publications

References 37 publications

Enterovirus infections are associated with the induction of β‐cell autoimmunity in a prospective birth cohort study

Enterovirus infections are associated with the induction of β‐cell autoimmunity in a prospective birth cohort study

Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.

Detection of a Low-Grade Enteroviral Infection in the Islets of Langerhans of Living Patients Newly Diagnosed With Type 1 Diabetes

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