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

• Published in: Diabetologia 2021-11, Vol.64 (11), p.2491-2501
• Main Authors: Oikarinen, Sami, Krogvold, Lars, Edwin, Bjørn, Buanes, Trond, Korsgren, Olle, Laiho, Jutta E., Oikarinen, Maarit, Ludvigsson, Johnny, Skog, Oskar, Anagandula, Mahesh, Frisk, Gun, Hyöty, Heikki, Dahl-Jørgensen, Knut
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; Adult; Biopsy; Cell culture; Cell Line; Cell lines; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - virology; Enterovirus; Enterovirus - genetics; Enterovirus - isolation & purification; Enterovirus Infections - virology; Enteroviruses; Feces - virology; Female; Genomes; Human Physiology; Humans; Internal Medicine; Islets of Langerhans - virology; Laparoscopy; Leukocytes (mononuclear); Male; Medical diagnosis; Medicine; Medicine & Public Health; Metabolic Diseases; Mucosa; Organs; Pancreas; Patients; Peripheral blood mononuclear cells; Persistent infection; Real-Time Polymerase Chain Reaction; Reverse transcription; RNA, Viral - genetics; RT-qPCR; Sequence; Sequence analysis; Type 1 diabetes; Viral RNA; Viruses; Young Adult
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-021-05525-0

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