Rotavirus Infection of Infant and Young Adult Nonobese Diabetic Mice Involves Extraintestinal Spread and Delays Diabetes Onset

Graham, Kerr; O’Donnell, Joanne A.; Tan, Yan; Sanders, Natalie L.; Carrington, Emma M.; Allison, Janette; Coulson, Barbara S.

doi:10.1128/jvi.00205-07

Cited by 45 publications

(63 citation statements)

References 82 publications

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“…Infection of adult NOD and NOD8.3 mice is asymptomatic and aviraemic, and direct pancreatic infection is not involved in acceleration of diabetes by RRV [13]. In contrast, RRV infection of infant NOD mice induces diarrhoea, viraemia and pancreatic infection and delays diabetes onset [16].…”

Section: Introductionmentioning

confidence: 99%

“…(unless otherwise indicated) of rotavirus, as before [13,16]. The inactivated RRV (I-RRV) dose was equivalent to 2×10 6 f.f.u.…”

Section: Methodsmentioning

confidence: 99%

“…Diarrhoea was not detected in any mouse during the first 14 days after inoculation. Mice were monitored weekly for diabetes, as before [16].…”

Section: Methodsmentioning

confidence: 99%

“…Rotavirus-specific antibody assays Endpoint antibody titres (total immunoglobulin: IgG, IgM and IgA combined) in sera collected at 21 days post inoculation were determined by ELISA using homologous rotavirus antigen and mockinfected-cell control antigen, as before [16]. Rotavirus capture antigens were standardised by chequerboard titration using monoclonal antibody RVA directed to rotavirus capsid protein, to ensure that titres were comparable between virus strains [26].…”

Section: Methodsmentioning

confidence: 99%

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Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

et al. 2012

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Aims/hypothesis Rotavirus infection in at-risk children correlates with production of serum autoantibodies indicative of type 1 diabetes progression. Oral infection with rhesus monkey rotavirus (RRV) accelerates diabetes onset in mice. This relates to their rotavirus-specific serum antibody titre and local pro-inflammatory cytokine induction without pancreatic infection. Our aim was to further investigate the roles of serum antibodies and viral extra-intestinal spread in diabetes acceleration by rotavirus. Methods Rotavirus-specific serum antibody production was detected by ELISA in diabetes-prone mice given either inactivated or low-dose RRV, in relation to their diabetes development. Serum anti-rotavirus antibody titres and infectious virus in lymph nodes were measured in mice given RRV or porcine rotavirus CRW-8. In lymph node cells, rotavirus antigen presence and immune activation were determined by flow cytometry, in conjunction with cytokine mRNA levels. Results Acceleration of diabetes by RRV required virus replication, which correlated with antibody presence. CRW-8 induced similar specific total immunoglobulin and IgA titres to those induced by RRV, but did not accelerate diabetes. RRV alone elicited specific serum IgG antibodies with a T helper (Th)1 bias, spread to regional lymph nodes and activated antigen-presenting cells at these sites. RRV increased Th1-specific cytokine expression in pancreatic lymph nodes. Diabetes onset was more rapid in the RRVinfected mice with the greater Th1 bias. Conclusions/interpretation Acceleration of murine diabetes by rotavirus is virus strain-specific and associated with virus spread to regional lymph nodes, activation of antigenpresenting cells at these sites and induction of a Th1-dominated antibody and cytokine response.

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Section: Introductionmentioning

confidence: 99%

“…(unless otherwise indicated) of rotavirus, as before [13,16]. The inactivated RRV (I-RRV) dose was equivalent to 2×10 6 f.f.u.…”

Section: Methodsmentioning

confidence: 99%

“…Diarrhoea was not detected in any mouse during the first 14 days after inoculation. Mice were monitored weekly for diabetes, as before [16].…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

et al. 2012

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“…This acceleration is dependent on the presence of insulitis, as diabetes development is delayed or unaffected following RRV infection of infant and young adult NOD mice [98]. Diabetes acceleration by RRV is associated with a minimal degree of intestinal inflammation and is independent of pancreatic infection [7,29].…”

Section: How Might Bystander Lymphocyte Activation Contribute To Diabmentioning

confidence: 99%

Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes

Pane

Coulson

2015

Diabetologia

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Viruses are considered to be potential key modulators of type 1 diabetes mellitus, with several possible mechanisms proposed for their modes of action. Here we discuss the evidence for virus involvement, including pancreatic infection and the induction of T cell-mediated molecular mimicry. A particular focus of this review is the further possibility that virus infection triggers bystander activation of pre-existing autoreactive lymphocytes. In this scenario, the virus triggers dendritic cell maturation and proinflammatory cytokine secretion by engaging pattern recognition receptors. These proinflammatory cytokines provoke bystander autoreactive lymphocyte activation in the presence of cognate autoantigen, which leads to enhanced beta cell destruction. Importantly, this mechanism does not necessarily involve pancreatic virus infection, and its virally non-specific nature suggests that it might represent a means commonly employed by multiple viruses. The ability of viruses specifically associated with type 1 diabetes, including group B coxsackievirus, rotavirus and influenza A virus, to induce these responses is also examined. The elucidation of a mechanism shared amongst several viruses for accelerating progression to type 1 diabetes would facilitate the identification of important targets for disease intervention.

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Association Between Rotavirus Vaccination and Type 1 Diabetes in Children

et al. 2020

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IMPORTANCE Because rotavirus infection is a hypothesized risk factor for type 1 diabetes, live attenuated rotavirus vaccination could increase or decrease the risk of type 1 diabetes in children.OBJECTIVE To examine whether there is an association between rotavirus vaccination and incidence of type 1 diabetes in children aged 8 months to 11 years. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study of 386 937 children born between January 1, 2006, and December 31, 2014, was conducted in 7 US health care organizations of the Vaccine Safety Datalink. Eligible children were followed up until a diagnosis of type 1 diabetes, disenrollment, or December 31, 2017.EXPOSURES Rotavirus vaccination for children aged 2 to 8 months. Three exposure groups were created. The first group included children who received all recommended doses of rotavirus vaccine by 8 months of age (fully exposed to rotavirus vaccination). The second group had received some, but not all, recommended rotavirus vaccines (partially exposed to rotavirus vaccination). The third group did not receive any doses of rotavirus vaccines (unexposed to rotavirus vaccination). MAIN OUTCOMES AND MEASURESIncidence of type 1 diabetes among children aged 8 months to 11 years. Type 1 diabetes was identified by International Classification of Diseases codes: 250.x1, 250.x3, or E10.xx in the outpatient setting. Cox proportional hazards regression models were used to analyze time to type 1 diabetes incidence from 8 months to 11 years. Hazard ratios and 95% CIs were calculated. Models were adjusted for sex, race/ethnicity, birth year, mother's age, birth weight, gestational age, number of well-child visits, and Vaccine Safety Datalink site. RESULTSIn a cohort of 386 937 children (51.1% boys and 41.9% non-Hispanic white), 360 169 (93.1%) were fully exposed to rotavirus vaccination, 15 765 (4.1%) were partially exposed to rotavirus vaccination, and 11 003 (2.8%) were unexposed to rotavirus vaccination. Children were followed up a median of 5.4 years (interquartile range, 3.8-7.8 years). The total person-time follow-up in the cohort was 2 253 879 years. There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20.6 cases per 100 000 person-years. Compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio was 1.03 (95% CI, 0.62-1.72) for children fully exposed to rotavirus vaccination and 1.50 (95% CI, 0.81-2.77) for children partially exposed to rotavirus vaccination. CONCLUSIONS AND RELEVANCEThe findings of this study suggest that rotavirus vaccination does not appear to be associated with type 1 diabetes in children.

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Rotavirus Infection of Infant and Young Adult Nonobese Diabetic Mice Involves Extraintestinal Spread and Delays Diabetes Onset

Cited by 45 publications

References 82 publications

Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes

Association Between Rotavirus Vaccination and Type 1 Diabetes in Children

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