Article: Coxsackievirus-B4 Infection of Human Primary Pancreatic Ductal Cell Cultures Results in Impairment of Differentiation into Insulin-Producing Cells
Viruses. 2019 July 02, v. 11, no. 7
2019
Abstract: Coxsackievirus-B4 (CV-B4) E2 can persist in the pancreatic ductal-like cells (Panc-1 cell line), which results in an impaired differentiation of these cells into islet-like cell aggregates (ICA). In this study, primary pancreatic ductal cells obtained as ...
| Abstract | Coxsackievirus-B4 (CV-B4) E2 can persist in the pancreatic ductal-like cells (Panc-1 cell line), which results in an impaired differentiation of these cells into islet-like cell aggregates (ICA). In this study, primary pancreatic ductal cells obtained as a by-product of islet isolation from the pancreas of seven brain-dead adults were inoculated with CV-B4 E2, followed-up for 29 days, and the impact was investigated. Viral titers in culture supernatants were analyzed throughout the culture. Intracellular viral RNA was detected by RT-PCR. Levels of ductal cell marker CK19 mRNA and of insulin mRNA were evaluated by qRT-PCR. The concentration of c-peptide in supernatants was determined by ELISA. Ductal cells exposed to trypsin and serum-free medium formed ICA and resulted in an increased insulin secretion. Ductal cells from five brain-dead donors were severely damaged by CV-B4 E2, whereas the virus persisted in cultures of cells obtained from the other two. The ICAs whose formation was induced on day 14 post-inoculation were scarce and appeared tiny in infected cultures. Also, insulin mRNA expression and c-peptide levels were strongly reduced compared to the controls. In conclusion, CV-B4 E2 lysed human primary pancreatic ductal cells or persisted in these cells, which resulted in the impairment of differentiation into insulin-producing cells. |
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| Keywords | adults ; byproducts ; c-peptide ; cell aggregates ; cell culture ; cell lines ; enzyme-linked immunosorbent assay ; gene expression ; humans ; insulin secretion ; messenger RNA ; pancreas ; quantitative polymerase chain reaction ; reverse transcriptase polymerase chain reaction ; trypsin ; viral load ; viruses |
| Language | English |
| Dates of publication | 2019-0702 |
| Publishing place | Multidisciplinary Digital Publishing Institute |
| Document type | Article |
| ZDB-ID | 2516098-9 |
| ISSN | 1999-4915 |
| ISSN | 1999-4915 |
| DOI | 10.3390/v11070597 |
| Database | NAL-Catalogue (AGRICOLA) |
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