Increased Level of Interferon‐α in Blood of Patients with Insulin‐Dependent Diabetes Mellitus: Relationship with Coxsackievirus B Infection

Chehadeh, Wassim; Weill, Jacques; Vantyghem, Marie-Christine; Alm, G.; Lefèbvre, J; Wattré, P; Hober, Didier

doi:10.1086/315516

Cited by 157 publications

(132 citation statements)

References 52 publications

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“…Our interest in the blood comes from the fact that enteroviral RNA of CVB subgroup members, especially CVB4, was detected in human blood from patients with type 1 diabetes with nucleotide sequence homologous to CVB4 E2 in some patients (6,20). In an experimental model based on inbred male SWR mice inoculated with CVB3 by the intraperitoneal route (16), viral RNA was detected by quantitative RT-PCR in blood up to day 14 p.i.…”

Section: Cd8mentioning

confidence: 99%

Prolonged Viral RNA Detection in Blood and Lymphoid Tissues from Coxsackievirus B4 E2 Orally‐Inoculated Swiss Mice

Jaïdane

Gharbi

Lobert

et al. 2006

Microbiology and Immunology

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Abstract:The spreading of viral RNA within Swiss Albino mice orally inoculated with coxsackievirus B4 E2 strain (CVB4 E2) was studied by using RT-PCR and semi-nested-RT-PCR methods. Viral RNA was detected in various organs: pancreas, heart, small intestine, spleen, thymus, and blood at various postinfectious (p.i.) times ranging from 8 hr to 150 days. Our results show that (i) outbred mice can be infected with CVB4 E2 following an oral inoculation, which results in systemic spreading of viral RNA, (ii) CVB4 E2 infection can be associated with a prolonged detection of viral RNA in spleen, thymus and blood, up to 70 days p.i. and further in other organ tissues.

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Section: Cd8mentioning

confidence: 99%

Prolonged Viral RNA Detection in Blood and Lymphoid Tissues from Coxsackievirus B4 E2 Orally‐Inoculated Swiss Mice

Jaïdane

Gharbi

Lobert

et al. 2006

Microbiology and Immunology

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“…Seroepidemiological data implicated largely enteroviruses, especially type B coxsackieviruses (CV-B), in type 1 diabetes development [Helfand et al, 1995;Hyöty et al, 1995] and several studies observed the presence of nucleotide sequences of those viruses in the blood of patients with that disease (reviewed by Hyöty et al, 2002). Among CV-B or enterovirus genus, CV-B4 is one of the serotypes most frequently associated with the disease in prediabetic and diabetic patients [Gamble et al, 1973;Chehadeh et al, 2000b]. The diabetogenic strain CV-B4 E2 was isolated from the pancreas of a child who died from diabetic ketoacidosis and was able to induce hyperglycaemia in some susceptible mouse strains [Yoon et al, 1979].…”

Section: Introductionmentioning

confidence: 99%

Coxsackievirus B4 infection of murine foetal thymus organ cultures

Brilot

Jaïdane

Geenen

et al. 2008

Journal of Medical Virology

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The infection of foetal thymus with coxsackievirus B4 (CV-B4) E2 has been studied ex vivo by using CD-1 mice on foetal day 14, as a ready source of organs for experimentation to investigate the hypothesis of the role of thymic viral infections in the pathogenesis of type 1 diabetes. The replication of CV-B4 E2 in murine foetal thymus organ cultures has been demonstrated by evaluating the levels of positive-and negativestranded viral RNA in cells by using a real-time quantitative RT-PCR method and by determining titres of infectious viral particles in culture supernatants for 7 days post-infection (p.i.). Staining of tissue sections with an anti-cytokeratin antibody and haematoxylin-eosin showed that CV-B4 infection had no visible effect on cell survival and organ integrity. Cell counts in mock-and virus-infected foetal thymus organ cultures increased from day 1 through day 7, and live cell numbers were comparable in both conditions as shown by Trypan blue exclusion test and 7-amino-actinomycin D staining of thymocytes. Compared with controls on day 7 p.i., cytofluorometric analyses on cells from CV-B4 E2-infected foetal thymus organ cultures displayed a marked increase in the percentage of the most immature CD3 À CD4 À CD8 À thymocytes, and a decrease in the percentage of immature CD3 À CD4 þ CD8 þ cells, together with an increase in the percentage of mature CD3 þ CD4 þ and CD3 þ CD8 þ cells. These data show that CV-B4 E2 disturbs T-cell maturation and differentiation processes in infected murine foetal thymus organ cultures and provide evidence of a suitable system to investigate the effect of viruses in T-cell differentiation.

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“…The process, which finally leads to complete beta-cell loss and onset of clinical disease, starts years before any clinical symptoms and is thought to result from several factors involving host genes, autoimmune responses and cytokines, as well as environmental factors. Results from previous cross-sectional and prospective studies on patients with Type 1 diabetes and/or prediabetic individuals have suggested that enterovirus infections are involved in the development of the disease [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15].…”

mentioning

confidence: 99%

Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells

Ylipaasto

Klingel

Lindberg³

et al. 2004

Diabetologia

261

248

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Aims/hypothesis. It is thought that enterovirus infections cause beta-cell damage and contribute to the development of Type 1 diabetes by replicating in the pancreatic islets. We sought evidence for this through autopsy studies and by investigating known enterovirus receptors in cultured human islets. Methods. Autopsy pancreases from 12 newborn infants who died of fulminant coxsackievirus infections and from 65 Type 1 diabetic patients were studied for presence of enteroviral ribonucleic acid by in situ hybridisation. Forty non-diabetic control pancreases were included in the study. The expression and role of receptor candidates in cultured human islets were investigated with receptor-specific antibodies using immunocytochemistry and functional assays. Results. Enterovirus-positive islet cells were found in some of both autopsy specimen collections, but not in control pancreases. No infected cells were seen in exocrine tissue. The cell surface molecules, poliovirus receptor and integrin αvβ 3 , which act as enterovirus receptors in established cell lines, were expressed in beta cells. Antibodies to poliovirus receptor, human coxsackievirus and adenovirus receptor and integrin αvβ 3 protected islets and beta cells from adverse effects of poliovirus, coxsackie B viruses, and several of the arginine-glycine-aspartic acid motifs containing enteroviruses and human parechovirus 1 respectively. No evidence was found for expression of the decay-accelerating factor which acts as a receptor for several isletcell-replicating echoviruses in established cell lines. Conclusions/interpretation. The results show a definite islet-cell tropism of enteroviruses in the human pancreas. Some enteroviruses seem to use previously identified cell surface molecules as receptors in beta cells, whereas the identity of receptors used by other enteroviruses remains unknown. [Diabetologia (2004) 47:225-239]

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Increased Level of Interferon‐α in Blood of Patients with Insulin‐Dependent Diabetes Mellitus: Relationship with Coxsackievirus B Infection

Cited by 157 publications

References 52 publications

Prolonged Viral RNA Detection in Blood and Lymphoid Tissues from Coxsackievirus B4 E2 Orally‐Inoculated Swiss Mice

Prolonged Viral RNA Detection in Blood and Lymphoid Tissues from Coxsackievirus B4 E2 Orally‐Inoculated Swiss Mice

Coxsackievirus B4 infection of murine foetal thymus organ cultures

Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells

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