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Echovirus 6 infects human exocrine and endocrine pancreatic cells and induces pro-inflammatory innate immune response

Sarmiento-Pérez, Luis LU orcid ; Frisk, Gun ; Anagandula, Mahesh ; Hodik, Monika ; Barchetta, Ilaria LU ; Netanyah, Eitan LU orcid ; Cabrera-Rode, Eduardo and Cilio, Corrado M. LU (2017) In Viruses 9(2).
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... (More)

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), 2ʹ-5ʹ-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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acinar cells, Echovirus, Enterovirus, Inflammation, Islet of Langerhans, Pancreas, Tropism
in
Viruses
volume
9
issue
2
article number
25
publisher
MDPI AG
external identifiers
  • scopus:85011706677
  • pmid:28146100
  • wos:000397251000003
ISSN
1999-4915
DOI
10.3390/v9020025
project
Unravelling the mechanistic link between enterovirus infection and type 1 diabetes
language
English
LU publication?
yes
id
1bd9635a-cbc9-4902-99c3-986d2137927c
date added to LUP
2017-02-20 10:41:13
date last changed
2025-01-07 07:37:36
@article{1bd9635a-cbc9-4902-99c3-986d2137927c,
  abstract     = {{<p>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), 2ʹ-5ʹ-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.</p>}},
  author       = {{Sarmiento-Pérez, Luis and Frisk, Gun and Anagandula, Mahesh and Hodik, Monika and Barchetta, Ilaria and Netanyah, Eitan and Cabrera-Rode, Eduardo and Cilio, Corrado M.}},
  issn         = {{1999-4915}},
  keywords     = {{Acinar cells; Echovirus; Enterovirus; Inflammation; Islet of Langerhans; Pancreas; Tropism}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  publisher    = {{MDPI AG}},
  series       = {{Viruses}},
  title        = {{Echovirus 6 infects human exocrine and endocrine pancreatic cells and induces pro-inflammatory innate immune response}},
  url          = {{http://dx.doi.org/10.3390/v9020025}},
  doi          = {{10.3390/v9020025}},
  volume       = {{9}},
  year         = {{2017}},
}