Expression of innate immunity genes and damage of primary human pancreatic islets by epidemic strains of echovirus: implication for post-virus islet autoimmunity.
Sarmiento-Pérez, Luis LU
; Frisk, Gun
; Anagandula, Mahesh
; Cabrera-Rode, Eduardo
; Roivainen, Merja
and Cilio, Corrado
LU
(2013)
In PLoS ONE
8(11).
- Abstract
- Three large-scale Echovirus (E) epidemics (E4,E16,E30), each differently associated to the acute development of diabetes related autoantibodies, have been documented in Cuba. The prevalence of islet cell autoantibodies was moderate during the E4 epidemic but high in the E16 and E30 epidemic. The aim of this study was to evaluate the effect of epidemic strains of echovirus on beta-cell lysis, beta-cell function and innate immunity gene expression in primary human pancreatic islets. Human islets from non-diabetic donors (n = 7) were infected with the virus strains E4, E16 and E30, all isolated from patients with aseptic meningitis who seroconverted to islet cell antibody positivity. Viral replication, degree of cytolysis, insulin release in... (More)
- Three large-scale Echovirus (E) epidemics (E4,E16,E30), each differently associated to the acute development of diabetes related autoantibodies, have been documented in Cuba. The prevalence of islet cell autoantibodies was moderate during the E4 epidemic but high in the E16 and E30 epidemic. The aim of this study was to evaluate the effect of epidemic strains of echovirus on beta-cell lysis, beta-cell function and innate immunity gene expression in primary human pancreatic islets. Human islets from non-diabetic donors (n = 7) were infected with the virus strains E4, E16 and E30, all isolated from patients with aseptic meningitis who seroconverted to islet cell antibody positivity. Viral replication, degree of cytolysis, insulin release in response to high glucose as well as mRNA expression of innate immunity genes (IFN-b, RANTES, RIG-I, MDA5, TLR3 and OAS) were measured. The strains of E16 and E30 did replicate well in all islets examined, resulting in marked cytotoxic effects. E4 did not cause any effects on cell lysis, however it was able to replicate in 2 out of 7 islet donors. Beta-cell function was hampered in all infected islets (P<0.05); however the effect of E16 and E30 on insulin secretion appeared to be higher than the strain of E4. TLR3 and IFN-beta mRNA expression increased significantly following infection with E16 and E30 (P<0.033 and P<0.039 respectively). In contrast, the expression of none of the innate immunity genes studied was altered in E4-infected islets. These findings suggest that the extent of the epidemic-associated islet autoimmunity may depend on the ability of the viral strains to damage islet cells and induce pro-inflammatory innate immune responses within the infected islets. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4179450
- author
- Sarmiento-Pérez, Luis
LU
; Frisk, Gun
; Anagandula, Mahesh
; Cabrera-Rode, Eduardo
; Roivainen, Merja
and Cilio, Corrado
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 8
- issue
- 11
- article number
- e77850
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000326499300010
- pmid:24223733
- scopus:84891441542
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0077850
- language
- English
- LU publication?
- yes
- id
- 89658b3f-cdf7-4e93-b0d6-af8e0fecba65 (old id 4179450)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24223733?dopt=Abstract
- date added to LUP
- 2016-04-01 14:19:34
- date last changed
- 2024-07-18 06:12:12
@article{89658b3f-cdf7-4e93-b0d6-af8e0fecba65,
abstract = {{Three large-scale Echovirus (E) epidemics (E4,E16,E30), each differently associated to the acute development of diabetes related autoantibodies, have been documented in Cuba. The prevalence of islet cell autoantibodies was moderate during the E4 epidemic but high in the E16 and E30 epidemic. The aim of this study was to evaluate the effect of epidemic strains of echovirus on beta-cell lysis, beta-cell function and innate immunity gene expression in primary human pancreatic islets. Human islets from non-diabetic donors (n = 7) were infected with the virus strains E4, E16 and E30, all isolated from patients with aseptic meningitis who seroconverted to islet cell antibody positivity. Viral replication, degree of cytolysis, insulin release in response to high glucose as well as mRNA expression of innate immunity genes (IFN-b, RANTES, RIG-I, MDA5, TLR3 and OAS) were measured. The strains of E16 and E30 did replicate well in all islets examined, resulting in marked cytotoxic effects. E4 did not cause any effects on cell lysis, however it was able to replicate in 2 out of 7 islet donors. Beta-cell function was hampered in all infected islets (P<0.05); however the effect of E16 and E30 on insulin secretion appeared to be higher than the strain of E4. TLR3 and IFN-beta mRNA expression increased significantly following infection with E16 and E30 (P<0.033 and P<0.039 respectively). In contrast, the expression of none of the innate immunity genes studied was altered in E4-infected islets. These findings suggest that the extent of the epidemic-associated islet autoimmunity may depend on the ability of the viral strains to damage islet cells and induce pro-inflammatory innate immune responses within the infected islets.}},
author = {{Sarmiento-Pérez, Luis and Frisk, Gun and Anagandula, Mahesh and Cabrera-Rode, Eduardo and Roivainen, Merja and Cilio, Corrado}},
issn = {{1932-6203}},
language = {{eng}},
number = {{11}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Expression of innate immunity genes and damage of primary human pancreatic islets by epidemic strains of echovirus: implication for post-virus islet autoimmunity.}},
url = {{https://lup.lub.lu.se/search/files/3912498/4359814.pdf}},
doi = {{10.1371/journal.pone.0077850}},
volume = {{8}},
year = {{2013}},
}