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Diabetologia
Published in: Diabetologia 6/2009

01-06-2009 | Article

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes

Authors: S. J. Richardson, A. Willcox, A. J. Bone, A. K. Foulis, N. G. Morgan

Published in: Diabetologia | Issue 6/2009

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Abstract

Aims/hypothesis

Evidence that the beta cells of human patients with type 1 diabetes can be infected with enterovirus is accumulating, but it remains unclear whether such infections occur at high frequency and are important in the disease process. We have now assessed the prevalence of enteroviral capsid protein vp1 (vp1) staining in a large cohort of autopsy pancreases of recent-onset type 1 diabetic patients and a range of controls.

Methods

Serial sections of paraffin-embedded pancreatic autopsy samples from 72 recent-onset type 1 diabetes patients and up to 161 controls were immunostained for insulin, glucagon, vp1, double-stranded RNA activated protein kinase R (PKR) and MHC class I.

Results

vp1-immunopositive cells were detected in multiple islets of 44 out of 72 young recent-onset type 1 diabetic patients, compared with a total of only three islets in three out of 50 neonatal and paediatric normal controls. vp1 staining was restricted to insulin-containing beta cells. Among the control pancreases, vp1 immunopositivity was also observed in some islets from ten out of 25 type 2 diabetic patients. A strong correlation was established between islet cell vp1 positivity and PKR production in insulin-containing islets of both type 1 and type 2 diabetic patients, consistent with a persistent viral infection of the islets.

Conclusions/interpretation

Immunoreactive vp1 is commonly found in the islets of recent-onset type 1 diabetes patients, but only rarely in normal paediatric controls. vp1 immunostaining was also observed in some islets of type 2 diabetes patients, suggesting that the phenomenon is not restricted to type 1 diabetes patients.
Appendix
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Literature
1.
Gale EAM (2008) Congenital rubella: citation virus or viral cause of type 1 diabetes? Diabetologia 51:1559–1566PubMedCrossRef
2.
Gamble DR, Kinsley ML, FitzGerald MG, Bolton R, Taylor KW (1969) Viral antibodies in diabetes mellitus. BMJ 3:627–630PubMedCrossRef
3.
Andreoletti L, Hober D, Hober-Vandenberghe C et al (1997) Detection of Coxsackie B virus RNA sequences in whole blood samples from adult patients at the onset of type I diabetes mellitus. J Med Virol 52:121–127PubMedCrossRef
4.
Clements GB, Galbraith DN, Taylor KW (1995) Coxsackie B virus infection and onset of childhood diabetes. Lancet 346:221–223PubMedCrossRef
5.
Coutant R, Carel JC, Lebon P, Bougneres PF, Palmer P, Cantero-Aguilar L (2002) Detection of enterovirus RNA sequences in serum samples from autoantibody-positive subjects at risk for diabetes. Diabet Med 19:968–969PubMedCrossRef
6.
Elfaitouri A, Berg AK, Frisk G, Yin H, Tuvemo T, Blomberg J (2007) Recent enterovirus infection in type 1 diabetes: evidence with a novel IgM method. J Med Virol 79:1861–1867PubMedCrossRef
7.
Moya-Suri V, Schlosser M, Zimmermann K, Rjasanowski I, Gurtler L, Mentel R (2005) Enterovirus RNA sequences in sera of schoolchildren in the general population and their association with type 1-diabetes-associated autoantibodies. J Med Microbiol 54:879–883PubMedCrossRef
8.
Nairn C, Galbraith DN, Taylor KW, Clements GB (1999) Enterovirus variants in the serum of children at the onset of Type 1 diabetes mellitus. Diabet Med 16:509–513PubMedCrossRef
9.
von Herrath M (2009) Can we learn from viruses how to prevent type 1 diabetes? The role of virus infections in the pathogenesis of type 1 diabetes and the development of novel combination therapies. Diabetes 58:2–11CrossRef
10.
Sarmiento L, Cabrera-Rode E, Lekuleni L et al (2007) Occurrence of enterovirus RNA in serum of children with newly diagnosed type 1 diabetes and islet cell autoantibody-positive subjects in a population with a low incidence of type 1 diabetes. Autoimmunity 40:540–545PubMedCrossRef
11.
Yoon JW, Austin M, Onodera T, Notkins AL (1979) Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 300:1173–1179PubMed
12.
Ylipaasto P, Klingel K, Lindberg AM et al (2004) Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells. Diabetologia 47:225–239PubMedCrossRef
13.
Dotta F, Censini S, van Halteren AG et al (2007) Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci U S A 104:5115–5120PubMedCrossRef
14.
Tam PE, Messner RP (1999) Molecular mechanisms of Coxsackie virus persistence in chronic inflammatory myopathy: viral RNA persists through formation of a double-stranded complex without associated genomic mutations or evolution. J Virol 73:10113–10121PubMed
15.
Ylipaasto P, Kutlu B, Rasilainen S et al (2005) Global profiling of Coxsackie virus- and cytokine-induced gene expression in human pancreatic islets. Diabetologia 48:1510–1522PubMedCrossRef
16.
Chehadeh W, Kerr-Conte J, Pattou F et al (2000) Persistent infection of human pancreatic islets by Coxsackie virus B is associated with alpha-interferon synthesis by beta-cells. J Virol 74:10153–10164PubMedCrossRef
17.
Foulis AK, Farquharson MA, Meager A (1987) Immunoreactive alpha-interferon in insulin-secreting beta cells in type 1 diabetes mellitus. Lancet 2:1423–1427PubMedCrossRef
18.
Foulis AK, Liddle CN, Farquharson MA et al (1986) The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom. Diabetologia 29:267–274PubMedCrossRef
19.
Oikarinen M, Tauriainen S, Honkanen T et al (2008) Analysis of pancreas tissue in a child positive for islet cell antibodies. Diabetologia 51:1796–1802PubMedCrossRef
20.
Oikarinen M, Tauriainen S, Honkanen T et al (2008) Detection of enteroviruses in the intestine of type 1 diabetic patients. Clin Exp Immunol 151:71–75PubMedCrossRef
21.
Andréoletti L, Bourlet T, Moukassa D et al (2000) Enteroviruses can persist with or without active viral replication in cardiac tissue of patients with end-stage ischemic or dilated cardiomyopathy. J Infect Dis 182:1222–1227PubMedCrossRef
22.
Triantafyllopoulou A, Tapinos N, Moutsopoulos HM (2004) Evidence for coxsackievirus infection in primary Sjögren's syndrome. Arthritis Rheum 50:2897–2902PubMedCrossRef
23.
Klingel K, Sauter M, Bock CT, Szalay G, Schnorr JJ, Kandolf R (2004) Molecular pathology of inflammatory cardiomyopathy. Medical Microbiol Immunol 193:101–107CrossRef
24.
Hilton DA, Day C, Pringle JH, Fletcher A, Chambers S (1992) Demonstration of the distribution of coxsackie virus RNA in neonatal mice by non-isotopic in situ hybridization. J Virol Methods 40:155–162PubMedCrossRef
25.
Härkönen T, Puolakkainen M, Sarvas M, Airaksinen U, Hovi T, Roivainen M (2000) Picornavirus proteins share antigenic determinants with heat shock proteins 60/65. J Med Virol 62:383–391PubMedCrossRef
26.
Härkönen T, Lankinen H, Davydova B, Hovi T, Roivainen M (2002) Enterovirus infection can induce immune responses that cross-react with beta-cell autoantigen tyrosine phosphatase IA-2/IAR. J Med Virol 66:340–350PubMedCrossRef
27.
Mallard K, Jones DB, Richmond J, McGill M, Foulis AK (1996) Expression of the human heat shock protein 60 in thyroid, pancreatic, hepatic and adrenal autoimmunity. J Autoimmun 9:89–96PubMedCrossRef
28.
Drescher KM, Tracy SM (2008) The CVB and etiology of type 1 diabetes. Curr Top Microbiol Immunol 323:259–274PubMedCrossRef
29.
Foulis AK, McGill M, Farquharson MA, Hilton DA (1997) A search for evidence of viral infection in pancreases of newly diagnosed patients with IDDM. Diabetologia 40:53–61PubMedCrossRef
30.
Everett H, McFadden G (1999) Apoptosis: an innate immune response to virus infection. Trends Microbiol 7:160–165PubMedCrossRef
31.
Foulis AK, Farquharson MA, Hardman R (1987) Aberrant expression of class II major histocompatibility complex molecules by B cells and hyperexpression of class I major histocompatibility complex molecules by insulin containing islets in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30:333–343PubMedCrossRef
32.
Klingel KC, Hohenadl C, Canu A et al (1992) Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage and inflammation. Proc Natl Acad Sci U S A 89:314–318PubMedCrossRef
33.
Ehses JA, Perren A, Eppler E et al (2007) Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56:2356–2370PubMedCrossRef
34.
Witso E, Palacios G, Cinek O et al (2006) High prevalence of human enterovirus a infections in natural circulation of human enteroviruses. J Clin Microbiol 44:4095–4100PubMedCrossRef
35.
Cinek O, Witso E, Jeansson S et al (2006) Longitudinal observation of enterovirus and adenovirus in stool samples from Norwegian infants with the highest genetic risk of type 1 diabetes. J Clin Virol 35:33–40PubMedCrossRef
36.
Roivainen M (2006) Enteroviruses: new findings on the role of enteroviruses in type 1 diabetes. Int J Biochem Cell Biol 38:721–725PubMedCrossRef
37.
Roivainen M, Knip M, Hyoty H et al (1998) Several different enterovirus serotypes can be associated with prediabetic autoimmune episodes and onset of overt IDDM. Childhood Diabetes in Finland (DiMe) Study Group. J Med Virol 56:74–78PubMedCrossRef
Metadata
Title
The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes
Authors
S. J. Richardson
A. Willcox
A. J. Bone
A. K. Foulis
N. G. Morgan
Publication date
01-06-2009
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 6/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1276-0

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