Searching peripheral blood mononuclear cells of children with viral respiratory tract infections preceding islet autoimmunity for viruses by high-throughput sequencing

Hippich, Markus; Oleynik, Alexandra; Jain, Komal; Winkler, Christiane; Ferreira, Ricardo C.; Bonifacio, Ezio; Ziegler, Anette‐Gabriele; Briese, Thomas

doi:10.1007/s00592-018-1138-7

Cited by 6 publications

(18 citation statements)

References 5 publications

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“…This includes a recent report from the All Babies in Southeast Sweden (ABIS) cohort, demonstrating that maternal RTIs during pregnancy, particularly in the third gestational month, significantly increase the risk of T1D in the offspring (OR 4.1, 95% CI 2.2–7.5; p < 0.001) [ 187 ]. Current data on the association of RTIs and T1D are limited to self-reported or clinically diagnosed history of infections, with molecular data for RTIs in IA/T1D cohort studies lacking [ 22 , 47 , 183 , 187 , 188 , 189 , 190 ]. The proposition of the respiratory tract as an alternate source of primary infection resulting in secondary pancreatic infection is not out of the question, with higher rates of RTI recently linked to increased risk of IA in at-risk children.…”

Section: Site Of Infection: Gut Pancreas and Respiratorymentioning

confidence: 99%

“…The most critical limitation of conventional NGS for virome applications is its poor sensitivity for eukaryotic viruses, due to signals drowned out by noise from an overwhelming background of non-viral or bacteriophage nucleic acid. In an attempt to boost the sensitivity specifically for vertebrate-infecting viruses, we and others have applied VirCapSeq-VERT to characterise the gut and blood virome of children with IA/T1D [ 188 , 205 ]. Through target enrichment, we observed greater than 3-fold higher overall positivity of viruses in children compared to the DIPP virome study and achieved high concordance with targeted qPCR results.…”

Section: Virome and T1dmentioning

confidence: 99%

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Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

et al. 2021

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For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, as well as mechanistic studies of virus-infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here, we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

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Section: Site Of Infection: Gut Pancreas and Respiratorymentioning

confidence: 99%

Section: Virome and T1dmentioning

confidence: 99%

Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

et al. 2021

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“…To significantly improve the sensitivity of virome detection by up to 10,000-fold [74], we and others applied a novel viral enrichment strategy (VirCapSeq-VERT) to characterise the virome of children with IA in the Viruses In the Genetically at Risk (VIGR) study [36] and BABYDIET [9]. The sensitivity and specificity for virus detection using this method is on par with targeted PCR, unlike other virome-sequencing methods that use physical enrichment, which are less sensitive [36,74].…”

Section: Virusesmentioning

confidence: 99%

Early-life factors contributing to type 1 diabetes

et al. 2019

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The incidence of type 1 diabetes has increased since the mid-twentieth century at a rate that is too rapid to be attributed to genetic predisposition alone. While the disease can occur at any age, mounting evidence from longitudinal cohort studies of at-risk children indicate that type 1 diabetes associated autoantibodies can be present from the first year of life, and that those who develop type 1 diabetes at a young age have a more aggressive form of the disease. This corroborates the hypothesis that environmental exposures in early life contribute to type 1 diabetes risk, whether related to maternal influences on the fetus during pregnancy, neonatal factors or later effects during infancy and early childhood. Studies to date show a range of environmental triggers acting at different time points, suggesting a multifactorial model of genetic and environmental factors in the pathogenesis of type 1 diabetes, which integrally involves a dialogue between the immune system and pancreatic beta cells. For example, breastfeeding may have a weak protective effect on type 1 diabetes risk, while use of an extensively hydrolysed formula does not. Additionally, exposure to being overweight pre-conception, both in utero and postnatally, is associated with increased risk of type 1 diabetes. Epidemiological, clinical and pathological studies in humans support a role for viral infections, particularly enteroviruses, in type 1 diabetes, but definitive proof is lacking. The role of the early microbiome and its perturbations in islet autoimmunity and type 1 diabetes is the subject of investigation in ongoing cohort studies. Understanding the interactions between environmental exposures and the human genome and metagenome, particularly across ethnically diverse populations, will be critical for the development of future strategies for primary prevention of type 1 diabetes.

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“…The most critical limitation of conventional NGS for virome applications is its poor sensitivity for eukaryotic viruses, due to signals drowned out by noise from an overwhelming background of non-viral or bacteriophage nucleic acid. In an attempt to boost the sensitivity specifically for vertebrate-infecting viruses, we and others have applied VirCapSeq-VERT to characterise the gut and blood virome of children with IA/T1D [184,201]. Through target enrichment, we observed greater than 3-fold higher overall positivity of viruses in children compared to the DIPP virome study and achieved high concordance with targeted qPCR results.…”

Section: Virome and T1dmentioning

confidence: 62%

“…This includes a recent report from the All Babies in Southeast Sweden (ABIS) cohort demonstrating that maternal RTIs during pregnancy, particularly in the third gestational month, significantly increase the risk of T1D in the offspring (OR 4.1, 95% CI 2.2-7.5; P < 0.001) [183]. Current data on the association of RTIs and T1D are limited to self-reported or clinically diagnosed history of infections, with molecular data for RTIs in IA/T1D cohort studies lacking [22,48,179,[183][184][185][186]. The proposition of the respiratory tract as an alternate source of primary infection resulting in secondary pancreatic infection is not out of the question, with higher rates of RTI recently linked to increased risk of IA in at-risk children.…”

Section: Site Of Infection: Gut Pancreas and Respiratorymentioning

confidence: 99%

Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

Isaacs¹,

Foskett²,

Maxwell³

et al. 2021

Preprint

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For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

show abstract

Searching peripheral blood mononuclear cells of children with viral respiratory tract infections preceding islet autoimmunity for viruses by high-throughput sequencing

Cited by 6 publications

References 5 publications

Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

Early-life factors contributing to type 1 diabetes

Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

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