دورية أكاديمية
أعرض في EDS

Live enteroviruses, but not other viruses, detected in human pancreas at the onset of type 1 diabetes in the DiViD study.

التفاصيل البيبلوغرافية
العنوان: Live enteroviruses, but not other viruses, detected in human pancreas at the onset of type 1 diabetes in the DiViD study.
المؤلفون: Krogvold L; Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. lars.krogvold@gmail.com.; Institute of Clinical Dentistry, Faculty of Dentistry, University of Oslo, Oslo, Norway. lars.krogvold@gmail.com., Genoni A; Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy., Puggioni A; Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy., Campani D; Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy., Richardson SJ; Islet Biology Group (IBEx), Exeter Centre of Excellence in Diabetes (EXCEED), University of Exeter College of Medicine and Health, Exeter, UK., Flaxman CS; Islet Biology Group (IBEx), Exeter Centre of Excellence in Diabetes (EXCEED), University of Exeter College of Medicine and Health, Exeter, UK., Edwin B; Department for HPB Surgery, Oslo University Hospital, Oslo, Norway., Buanes T; Department for HPB Surgery, Oslo University Hospital, Oslo, Norway., Dahl-Jørgensen K; Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Toniolo A; Global Virus Network, University of Insubria, Varese, Italy.
المصدر: Diabetologia [Diabetologia] 2022 Dec; Vol. 65 (12), pp. 2108-2120. Date of Electronic Publication: 2022 Aug 12.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0006777 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0428 (Electronic) Linking ISSN: 0012186X NLM ISO Abbreviation: Diabetologia Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Berlin Springer Verlag
مواضيع طبية MeSH: Diabetes Mellitus, Type 1*/pathology , Epstein-Barr Virus Infections*/genetics , Epstein-Barr Virus Infections*/pathology , Enterovirus*/genetics , Enterovirus Infections*, Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; 5' Untranslated Regions ; Herpesvirus 4, Human/genetics ; Pancreas/pathology ; Real-Time Polymerase Chain Reaction ; Antigens, Viral ; Pancreatic Extracts
مستخلص: Aims/hypothesis: Enterovirus (EV) infection of pancreatic islet cells is one possible factor contributing to type 1 diabetes development. We have reported the presence of EV genome by PCR and of EV proteins by immunohistochemistry in pancreatic sections. Here we explore multiple human virus species in the Diabetes Virus Detection (DiViD) study cases using innovative methods, including virus passage in cell cultures.
Methods: Six recent-onset type 1 diabetes patients (age 24-35) were included in the DiViD study. Minimal pancreatic tail resection was performed under sterile conditions. Eleven live cases (age 43-83) of pancreatic carcinoma without diabetes served as control cases. In the present study, we used EV detection methods that combine virus growth in cell culture, gene amplification and detection of virus-coded proteins by immunofluorescence. Pancreas homogenates in cell culture medium were incubated with EV-susceptible cell lines for 3 days. Two to three blind passages were performed. DNA and RNA were extracted from both pancreas tissue and cell cultures. Real-time PCR was used for detecting 20 different viral agents other than EVs (six herpesviruses, human polyomavirus [BK virus and JC virus], parvovirus B19, hepatitis B virus, hepatitis C virus, hepatitis A virus, mumps, rubella, influenza A/B, parainfluenza 1-4, respiratory syncytial virus, astrovirus, norovirus, rotavirus). EV genomes were detected by endpoint PCR using five primer pairs targeting the partially conserved 5' untranslated region genome region of the A, B, C and D species. Amplicons were sequenced. The expression of EV capsid proteins was evaluated in cultured cells using a panel of EV antibodies.
Results: Samples from six of six individuals with type 1 diabetes (cases) and two of 11 individuals without diabetes (control cases) contained EV genomes (p<0.05). In contrast, genomes of 20 human viruses other than EVs could be detected only once in an individual with diabetes (Epstein-Barr virus) and once in an individual without diabetes (parvovirus B19). EV detection was confirmed by immunofluorescence of cultured cells incubated with pancreatic extracts: viral antigens were expressed in the cytoplasm of approximately 1% of cells. Notably, infection could be transmitted from EV-positive cell cultures to uninfected cell cultures using supernatants filtered through 100 nm membranes, indicating that infectious agents of less than 100 nm were present in pancreases. Due to the slow progression of infection in EV-carrying cell cultures, cytopathic effects were not observed by standard microscopy but were recognised by measuring cell viability. Sequences of 5' untranslated region amplicons were compatible with EVs of the B, A and C species. Compared with control cell cultures exposed to EV-negative pancreatic extracts, EV-carrying cell cultures produced significantly higher levels of IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP1).
Conclusions/interpretation: Sensitive assays confirm that the pancreases of all DiViD cases contain EVs but no other viruses. Analogous EV strains have been found in pancreases of two of 11 individuals without diabetes. The detected EV strains can be passaged in series from one cell culture to another in the form of poorly replicating live viruses encoding antigenic proteins recognised by multiple EV-specific antibodies. Thus, the early phase of type 1 diabetes is associated with a low-grade infection by EVs, but not by other viral agents.
(© 2022. The Author(s).)
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معلومات مُعتمدة: MR/P010695/1 United Kingdom MRC_ Medical Research Council
فهرسة مساهمة: Keywords: Biopsy; Cell culture; Enterovirus; Gene amplification; Immunofluorescence; Pancreas; Type 1 diabetes
المشرفين على المادة: 0 (5' Untranslated Regions)
0 (Antigens, Viral)
0 (Pancreatic Extracts)
تواريخ الأحداث: Date Created: 20220811 Date Completed: 20221104 Latest Revision: 20230109
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9630231
DOI: 10.1007/s00125-022-05779-2
PMID: 35953727
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-0428
DOI:10.1007/s00125-022-05779-2