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Viruses 2017, 9(2), 25; doi:10.3390/v9020025

Echovirus 6 Infects Human Exocrine and Endocrine Pancreatic Cells and Induces Pro-Inflammatory Innate Immune Response

1
Cellular Autoimmunity Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Jan Waldenströms gata 35, CRC 91:10 205 02 Malmö, Sweden
2
Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, 75185 Uppsala, Sweden
3
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, 00185 Rome, Italy
4
Department of Immunology and Genetics on Diabetes, National Institute of Endocrinology, 10400 Havana, Cuba
*
Author to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 25 October 2016 / Revised: 5 January 2017 / Accepted: 16 January 2017 / Published: 30 January 2017
(This article belongs to the Section Animal Viruses)
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Abstract

Human enteroviruses (HEV), especially coxsackievirus serotype B (CVB) and echovirus (E), have been associated with diseases of both the exocrine and endocrine pancreas, but so far evidence on HEV infection in human pancreas has been reported only in islets and ductal cells. This study aimed to investigate the capability of echovirus strains to infect human exocrine and endocrine pancreatic cells. Infection of explanted human islets and exocrine cells with seven field strains of E6 caused cytopathic effect, virus titer increase and production of HEV protein VP1 in both cell types. Virus particles were found in islets and acinar cells infected with E6. No cytopathic effect or infectious progeny production was observed in exocrine cells exposed to the beta cell-tropic strains of E16 and E30. Endocrine cells responded to E6, E16 and E30 by upregulating the transcription of interferon-induced with helicase C domain 1 (IF1H1), 2'-5'-oligoadenylate synthetase 1 (OAS1), interferon-β (IFN-β), chemokine (C–X–C motif) ligand 10 (CXCL10) and chemokine (C–C motif) ligand 5 (CCL5). Echovirus 6, but not E16 or E30, led to increased transcription of these genes in exocrine cells. These data demonstrate for the first time that human exocrine cells represent a target for E6 infection and suggest that certain HEV serotypes can replicate in human pancreatic exocrine cells, while the pancreatic endocrine cells are permissive to a wider range of HEV. View Full-Text
Keywords: acinar cells; echovirus; enterovirus; inflammation; islet of Langerhans; pancreas; tropism acinar cells; echovirus; enterovirus; inflammation; islet of Langerhans; pancreas; tropism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sarmiento, L.; Frisk, G.; Anagandula, M.; Hodik, M.; Barchetta, I.; Netanyah, E.; Cabrera-Rode, E.; Cilio, C.M. Echovirus 6 Infects Human Exocrine and Endocrine Pancreatic Cells and Induces Pro-Inflammatory Innate Immune Response. Viruses 2017, 9, 25.

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