Characterisation of enterovirus RNA detected in the pancreas and other specimens of live patients with newly diagnosed type 1 diabetes in the DiViD study

Sami Oikarinen, Lars Krogvold, Bjørn Edwin, Trond Buanes, Olle Korsgren, Jutta E. Laiho, Maarit Oikarinen, Johnny Ludvigsson, Oskar Skog, Mahesh Anagandula, Gun Frisk, Heikki Hyöty, Knut Dahl-Jørgensen

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Abstract

Aims/hypothesis: The Diabetes Virus Detection (DiViD) study is the first study to laparoscopically collect pancreatic tissue and purified pancreatic islets together with duodenal mucosa, serum, peripheral blood mononuclear cells (PBMCs) and stools from six live adult patients (age 24–35 years) with newly diagnosed type 1 diabetes. The presence of enterovirus (EV) in the pancreatic islets of these patients has previously been reported. Methods: In the present study we used reverse transcription quantitative real-time PCR (RT-qPCR) and sequencing to characterise EV genomes present in different tissues to understand the nature of infection in these individuals. Results: All six patients were found to be EV-positive by RT-qPCR in at least one of the tested sample types. Four patients were EV-positive in purified islet culture medium, three in PBMCs, one in duodenal biopsy and two in stool, while serum was EV-negative in all individuals. Sequencing the 5′ untranslated region of these EVs suggested that all but one belonged to enterovirus B species. One patient was EV-positive in all these sample types except for serum. Sequence analysis revealed that the virus strain present in the isolated islets of this patient was different from the strain found in other sample types. None of the islet-resident viruses could be isolated using EV-permissive cell lines. Conclusions/interpretation: EV RNA can be frequently detected in various tissues of patients with type 1 diabetes. At least in some patients, the EV strain in the pancreatic islets may represent a slowly replicating persisting virus. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
JournalDIABETOLOGIA
DOIs
Publication statusE-pub ahead of print - Aug 2021
Publication typeA1 Journal article-refereed

Keywords

  • Enterovirus
  • Laparoscopy
  • Organs
  • Pancreas
  • Persistent infection
  • RT-qPCR
  • Sequence
  • Type 1 diabetes
  • Viral RNA

Publication forum classification

  • Publication forum level 2

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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