Diabetes Acceleration or Prevention by a Coxsackievirus B4 Infection: Critical Requirements for both Interleukin-4 and Gamma Interferon

Serreze, David; Wasserfall, Clive; Ottendorfer, Eric W.; Stalvey, Michael S.; Pierce, Melissa A.; Gauntt, Charles J.; O'Donnell, Brian J.; Flanagan, James; Campbell-Thompson, Martha; Ellis, T. M.; Atkinson, Mark A.

doi:10.1128/jvi.79.2.1045-1052.2005

Cited by 65 publications

(54 citation statements)

References 32 publications

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“…Prevention of lethal CVB1 infection by a prior CVB3 infection has also been observed in a mouse model, fitting nicely with the findings in the current study (38). In addition to crossprotection, other mechanisms related to the induction of b-cell tolerance may mediate the protective effect of viruses against type 1 diabetes as described in NOD mice (39,40). In both cases, the close relationship between the protective and the diabetogenic serotypes suggests a particular impact of the CVB group enteroviruses on the risk of diabetes.…”

Section: Discussionsupporting

confidence: 76%

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Laitinen¹,

Honkanen

Pakkanen³

et al. 2014

Diabetes

230

221

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The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study. The study participants comprised 183 case children testing persistently positive for at least two diabetes-predictive autoantibodies and 366 autoantibody-negative matched control children. Coxsackievirus B1 was associated with an increased risk of β-cell autoimmunity. This risk was strongest when infection occurred a few months before autoantibodies appeared and was attenuated by the presence of maternal antibodies against the virus. Two other coxsackieviruses, B3 and B6, were associated with a reduced risk, with an interaction pattern, suggesting immunological cross-protection against coxsackievirus B1. These results support previous observations suggesting that the group B coxsackieviruses are associated with the risk of type 1 diabetes. The clustering of the risk and protective viruses to this narrow phylogenetic lineage supports the biological plausibility of this phenomenon.

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Section: Discussionsupporting

confidence: 76%

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Laitinen¹,

Honkanen

Pakkanen³

et al. 2014

Diabetes

230

221

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“…Diabetes development after enterovirus infection in the most commonly used experimental model, the NOD mouse, is dependent on the already established prediabetic phase including insulitis [15][16][17]31], which in the NOD mouse occurs after maternally transferred antibodies may have waned [32]. This is in contrast with humans in whom islet autoantibodies may already appear before the disappearance of maternal antibodies [23,33,34].…”

Section: Discussioncontrasting

confidence: 42%

“…[6,12]). Furthermore, experimental animal models have indicated that enterovirus infections can cause direct beta cell damage [13,14] and alter disease progression in the NOD mouse model [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

et al. 2013

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Aims/hypothesis Enterovirus (e.g. Coxsackie B virus serotypes [CVBs]) infections may be associated with development of type 1 diabetes. Studies conducted in several European countries have, however, shown an inverse correlation between the incidence of type 1 diabetes and the prevalence of enterovirus infections. These findings could in part be explained by an extension of the poliovirus hypothesis, suggesting that the absence of maternally transferred antibodies protecting offspring from early infection increases the risk for diabetes development. Experimental evidence supporting this hypothesis in type 1 diabetes is, however, lacking. As maternally transferred protection from infection is a crucial component of the extended poliovirus hypothesis, we here tested the hypothesis that previously infected females transfer protection against infection and diabetes to offspring.Methods The induction of CVB-specific maternal antibodies and transfer of protection from virus infection, replication and development of virus-induced diabetes to offspring was assessed using NOD and Socs1-transgenic NOD mice. Results Infected mice produced neutralising antibodies to CVB. Offspring from infected females were positive for neutralising antibodies and were strongly protected from both infection and experimental diabetes. Conclusions/interpretation Our study shows that maternally transferred antibodies protect offspring from enterovirus infection and virus-induced diabetes. This suggests that the absence of maternally provided protection increases the risk for severe outcomes after an enterovirus infection in offspring. Moreover, our findings may have implications for the design of prospective studies aimed at investigating the possible role of enterovirus infections in the aetiology of human type 1 diabetes.

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“…All samples, including those showing negative results for CVB4 E2 RNA, were positive for GAPDH mRNA, proving the RNA integrity and the absence of reaction inhibitors (results not shown). Our data show that a systemic spreading of CVB4 E2 following oral inoculation is possible and that outbred mice, in addition to inbred, diabetic, immuno-compromised or transgenic mice (4,8,9,11,18,21), can be infected with that viral strain. The natural expression in the mouse of a coxsackievirus and adenovirus receptor strongly homologous to the human one (19), made possible the use of these animals as models to study the infection with CVB4 E2.…”

mentioning

confidence: 98%

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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Diabetes Acceleration or Prevention by a Coxsackievirus B4 Infection: Critical Requirements for both Interleukin-4 and Gamma Interferon

Abstract: Type 1 diabetes acceleration in nonobese diabetic (NOD) mice through coxsackievirus B4 (CVB4) infection requires a preexisting critical mass of autoreactive T cells in pancreatic islets

Cited by 65 publications

References 32 publications

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

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

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