We review type 1 diabetes and host genetic components, as well as epigenetics and viruses associated with type 1 diabetes, with added emphasis on the enteroviruses, which are often associated with triggering the disease. Genus Enterovirus is classified into twelve species of which seven (Enterovirus A, Enterovirus B, Enterovirus C, and Enterovirus D and Rhinovirus A, Rhinovirus B, and Rhinovirus C) are human pathogens. These viruses are transmitted mainly by the fecal-oral route; they may also spread via the nasopharyngeal route. Enterovirus infections are highly prevalent, but these infections are usually subclinical or cause a mild flu-like illness. However, infections caused by enteroviruses can sometimes be serious, with manifestations of meningoencephalitis, paralysis, myocarditis, and in neonates a fulminant sepsis-like syndrome. These viruses are often implicated in chronic (inflammatory) diseases as chronic myocarditis, chronic pancreatitis, and type 1 diabetes. In this review we discuss the currently suggested mechanisms involved in the viral induction of type 1 diabetes. We recapitulate current basic knowledge and definitions. 1. History of Diabetes Symptoms of type 1 diabetes (T1D) have been recognized since approximately 1500?BC, when they were described on Egyptian papyrus as indicators of a rare disease that caused patients to lose weight rapidly and experience “too great emptying of the urine” [1, 2]. This was probably the first mention of the disease. At approximately the same time, however, Indian physicians realized that the urine of some patients attracted ants. These doctors classified the disease and named it “madhumeha” or “honey urine” [3]. Later, the disease was called “diabetes” by Greek physician Aretaeus, who noted symptoms such as constant thirst, excessive urination, and loss of weight. “Diabetes” comes from the Greek word for “siphon” (to draw off or convey liquid). The Arabian physician Avicenna (980–1037) was the first to bring attention to the complexity and progression of the disease, recognizing primary and secondary diabetes. In the 17th century, the Latin term “mellitus” meaning “honeyed” or “sweet” was added by Thomas Willis, an English physician, in his treatise Pharmaceutice Rationalis?(1674). He tested urine samples of patients to determine the presence of diabetes; those samples with a sweet taste indicated diabetes mellitus or “honeyed” diabetes. In 1776, Matthew Dobson measured the quantity of glucose in the urine samples of diabetic patients. Dr. Frederick Allen, a diabetes specialist in the early 20th
References
[1]
N. S. Papaspyros, “The history of diabetes,” in The History of Diabetes Mellitus, G. T. Verlag, Ed., p. 4, Thieme, Stuttgart, Germany, 1964.
[2]
http://www.crystalinks.com/egyptmedicine.html.
[3]
J. Zajac, A. Shrestha, P. Patel, and L. Poretsky, “The main events in the history of diabetes mellitus,” in Principles of Diabetes Mellitus, L. Poretsky, Ed., pp. 3–16, Springer, New York, NY, USA, 2nd edition, 2010.
[4]
F. Allen, “Studies concerning diabetes,” Journal of American Medical Association, vol. 63, pp. 939–943, 1914.
[5]
http://www.nobelprize.org/nobel_prizes/medicine/.
[6]
H. P. Himsworth, “The mechanism of diabetes mellitus,” The Lancet, vol. 234, no. 6047, pp. 171–176, 1939.
[7]
American Diabetes Association, “Standards of medical care in diabetes—2014,” Diabetes Care, vol. 37, no. 1, pp. 14–80, 2014.
[8]
World Health Organization, “Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy,” WHO/NMH/MND/13.2, World Health Organization, 2013.
[9]
“Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia,” Report of a WHO/IDF Consultation, 2006.
[10]
W. Gepts, “Pathologic anatomy of the pancreas in juvenile diabetes mellitus.,” Diabetes, vol. 14, no. 10, pp. 619–633, 1965.
[11]
A. K. Foulis, C. N. Liddle, M. A. Farquharson, J. A. Richmond, and R. S. Weir, “The histopathology of the pancreas in type I (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom,” Diabetologia, vol. 29, no. 5, pp. 267–274, 1986.
[12]
American Diabetes Association, “Diagnosis and classification of diabetes mellitus,” Diabetes Care, vol. 36, no. 1, pp. 67–74, 2013.
[13]
S. Baekkeskov, H.-J. Aanstoot, S. Christgau et al., “Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase,” Nature, vol. 347, no. 6289, pp. 151–156, 1990.
[14]
J. P. Palmer, C. M. Asplin, P. Clemons et al., “Insulin antibodies in insulin-dependent diabetics before insulin treatment,” Science, vol. 222, no. 4630, pp. 1337–1339, 1983.
[15]
E. Bonifacio, V. Lampasona, S. Genovese, M. Ferrari, and E. Bosi, “Identification of protein tyrosine phosphatase-like IA2 (islet cell antigen 512) as the insulin-dependent diabetes-related 37/40K autoantigen and a target of islet-cell antibodies,” The Journal of Immunology, vol. 155, no. 11, pp. 5419–5426, 1995.
[16]
J. Lu, Q. Li, H. Xie et al., “Identification of a second transmembrane protein tyrosine phosphatase, IA-2β, as an autoantigen in insulin-dependent diabetes mellitus: Precursor of the 37-kDa tryptic fragment,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 6, pp. 2307–2311, 1996.
[17]
M. Pietropaolo, L. Casta?o, S. Babu et al., “Islet cell autoantigen 69 kD (ICA69): molecular cloning and characterization of a novel diabetes-associated autoantigen,” The Journal of Clinical Investigation, vol. 92, no. 1, pp. 359–371, 1993.
[18]
L. Casta?o, E. Russo, L. Zhou, M. A. Lipes, and G. S. Eisenbarth, “Identification and cloning of a granule autoantigen (carboxypeptidase-H) associated with type I diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 73, no. 6, pp. 1197–1201, 1991.
[19]
R. C. Nayak, M. A. Omar, A. Rabizadeh, S. Srikanta, and G. S. Eisenbarth, ““Cytoplasmic” islet cell antibodies. Evidence that the target antigen is a sialoglycoconjugate,” Diabetes, vol. 34, no. 6, pp. 617–619, 1985.
[20]
S. D. Arden, B. O. Roep, P. I. Neophytou, et al., “Imogen 38: a novel 38-kD islet mitochondrial autoantigen recognized by T cells from a newly diagnosed type 1 diabetic patient,” The Journal of Clinical Investigation, vol. 97, no. 2, pp. 551–561, 1996.
[21]
H. Kasimiotis, M. A. Myers, A. Argentaro et al., “Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets,” Diabetes, vol. 49, no. 4, pp. 555–561, 2000.
[22]
J. M. Wenzlau, K. Juhl, L. Yu et al., “The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 43, pp. 17040–17045, 2007.
[23]
T. Kimpim?ki, A. Kupila, A.-M. H?m?l?inen et al., “The first signs of β-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the finnish type 1 diabetes prediction and prevention study,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 10, pp. 4782–4788, 2001.
[24]
C. F. Verge, R. Gianani, E. Kawasaki et al., “Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies,” Diabetes, vol. 45, no. 3, pp. 926–933, 1996.
[25]
G. F. Bottazzo, A. F. Christensen, and D. Doniach, “Islet cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies,” The Lancet, vol. 2, no. 7892, pp. 1279–1283, 1974.
[26]
D. P. Singal and M. A. Blajchman, “Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus,” Diabetes, vol. 22, no. 6, pp. 429–432, 1973.
[27]
A. G. Cudworth and J. C. Woodrow, “Letter: HL-A antigens and diabetes mellitus,” The Lancet, vol. 2, no. 7889, article 1153, 1974.
[28]
L. Zhang and G. S. Eisenbarth, “Prediction and prevention of type 1 diabetes mellitus,” Journal of Diabetes, vol. 3, no. 1, pp. 48–57, 2011.
[29]
D. J. Smyth, J. D. Cooper, R. Bailey et al., “A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region,” Nature Genetics, vol. 38, no. 6, pp. 617–619, 2006.
[30]
Genomes Project Consortium, “A map of human genome variation from population-scale sequencing,” Nature, vol. 467, no. 7319, pp. 1061–1073, 2010.
[31]
I. Kockum, C. B. Sanjeevi, S. Eastman, M. Landin-Olsson, G. Dahlquist, and ?. Lernmark, “Complex interaction between HLA DR and DQ in conferring risk for childhood type 1 diabetes,” European Journal of Immunogenetics, vol. 26, no. 5, pp. 361–372, 1999.
[32]
B. P. C. Koeleman, B. A. Lie, D. E. Undlien et al., “Genotype effects and epistasis in type 1 diabetes and HLA-DQ trans dimer associations with disease,” Genes and Immunity, vol. 5, no. 5, pp. 381–388, 2004.
[33]
O. L. Griffith, S. B. Montgomery, B. Bernier et al., “ORegAnno: an open-access community-driven resource for regulatory annotation,” Nucleic Acids Research, vol. 36, no. 1, pp. D107–D113, 2008.
[34]
J. K. Distefano and D. M. Taverna, “Technological issues and experimental design of gene association studies,” Methods in Molecular Biology, vol. 700, pp. 3–16, 2011.
[35]
H. A. Erlich, A. M. Valdes, S. L. McDevitt et al., “Next generation sequencing reveals the association of DRB3*02:02 with type 1 diabetes,” Diabetes, vol. 62, no. 7, pp. 2618–2622, 2013.
[36]
G. D. Snell and G. F. Higgins, “Alleles at the histocompatibility-2 locus in the mouse as determined by tumor transplantation,” Genetics, vol. 36, no. 3, pp. 306–310, 1951.
[37]
J. A. Noble and H. A. Erlich, “Genetics of type 1 diabetes,” Cold Spring Harbor Perspectives in Medicine, vol. 2, no. 1, Article ID a007732, 2012.
[38]
I. Santin and D. L. Eizirik, “Candidate genes for type 1 diabetes modulate pancreatic islet inflammation and β-cell apoptosis,” Diabetes, Obesity and Metabolism, vol. 15, no. 3, pp. 71–81, 2013.
[39]
The MHC sequencing consortium, “Complete sequence and gene map of a human major histocompatibility complex,” Nature, vol. 401, no. 6756, pp. 921–923, 1999.
[40]
B. Mach, V. Steimle, E. Martinez-Soria, and W. Reith, “Regulation of MHC class II genes: lessons from a disease,” Annual Review of Immunology, vol. 14, pp. 301–331, 1996.
[41]
V. Radha, K. S. Vimaleswaran, R. Deepa, and V. Mohan, “The genetics of diabetes mellitus,” Indian Journal of Medical Research, vol. 117, pp. 225–238, 2003.
[42]
H. A. Erlich, R. L. Griffith, T. L. Bugawan, R. Ziegler, C. Alper, and G. Eisenbarth, “Implication of specific DQB1 alleles in genetic susceptibility and resistance by identification of IDDM siblings with novel HLA-DQB1 allele and unusual DR2 and DR1 haplotypes,” Diabetes, vol. 40, no. 4, pp. 478–481, 1991.
[43]
D. J. Penn, “Major Histocompatibility Complex (MHC),” in Encyclopedia of Life Sciences, Macmillan Publishers Ltd, Nature Publishing Group, 2002.
[44]
J. R. Gruen and S. M. Weissman, “Human MHC class III and IV genes and disease associations,” Frontiers in Bioscience, vol. 6, pp. D960–D972, 2001.
[45]
J. Bell, “Perinatal diagnosis current approaches and future trends,” in Human Genetic Information: Science, Law and Ethics, CIBA Foundation Symposium 149, pp. 18–36, John Wiley & Sons, Chichester, UK, 1990.
[46]
R. Redon, S. Ishikawa, K. R. Fitch, et al., “Global variation in copy number in the human genome,” Nature, vol. 444, no. 7118, pp. 444–454, 2006.
[47]
R. Tisch and H. McDevitt, “Insulin-dependent diabetes mellitus,” Cell, vol. 85, no. 3, pp. 291–297, 1996.
[48]
E.-P. Reich, H. von Grafenstein, A. Barlow, K. E. Swenson, K. Williams, and C. A. Janeway Jr., “Self peptides isolated from MHC glycoproteins of non-obese diabetic mice,” The Journal of Immunology, vol. 152, no. 5, pp. 2279–2288, 1994.
[49]
A. P. Lambert, K. M. Gillespie, G. Thomson et al., “Absolute risk of childhood-onset type 1 diabetes defined by human leukocyte antigen class II genotype: a population-based study in the United Kingdom,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 8, pp. 4037–4043, 2004.
[50]
J. A. Noble, A. M. Valdes, M. Cook, W. Klitz, G. Thomson, and H. A. Erlich, “The role of HLA class II genes in insulin-dependent diabetes mellitus: Molecular analysis of 180 Caucasian, multiplex families,” American Journal of Human Genetics, vol. 59, no. 5, pp. 1134–1148, 1996.
[51]
J. C. Gorga and D. Monos, “HLA and disease: molecular basis,” in MHC Molecules: Expression, Assembly and Function, J. C. Gorga, Ed., pp. 135–162, Springer eBook, R. G. Landes Company, Austin, Tex, USA, 1996.
[52]
R. Horton, R. Gibson, P. Coggill et al., “Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype project,” Immunogenetics, vol. 60, no. 1, pp. 1–18, 2008.
[53]
D. F. Conrad, T. D. Andrews, N. P. Carter, M. E. Hurles, and J. K. Pritchard, “A high-resolution survey of deletion polymorphism in the human genome,” Nature Genetics, vol. 38, no. 1, pp. 75–81, 2006.
[54]
H. Beyan, R. C. Drexhage, L. V. D. H. Nieuwenhuijsen et al., “Monocyte gene-expression profiles associated with childhood-onset type 1 diabetes and disease risk: a study of identical twins,” Diabetes, vol. 59, no. 7, pp. 1751–1755, 2010.
[55]
C. Sapienza and J. G. Hall, “Genetic imprinting in human disease,” in The Metabolic and Molecular Bases of Inherited Disease, C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, Eds., vol. 1, chapter 7, pp. 437–458, McGraw-Hill, New York, NY, USA, 7th edition, 1995.
[56]
J. H. Warram, A. S. Krolewski, M. S. Gottlieb, and C. R. Kahn, “Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers,” The New England Journal of Medicine, vol. 311, no. 3, pp. 149–152, 1984.
[57]
H. Tillil and J. Kobberling, “Age-corrected empirical genetic risk estimates for first-degree relatives of IDDM patients,” Diabetes, vol. 36, no. 1, pp. 93–99, 1987.
[58]
D. Bleich, M. Polak, G. S. Eisenbarth, and R. A. Jackson, “Decreased risk of type I diabetes in offspring of mothers who acquire diabetes during adrenarchy,” Diabetes, vol. 42, no. 10, pp. 1433–1439, 1993.
[59]
L. Yu, H. P. Chase, A. Falorni, M. Rewers, ?. Lernmark, and G. S. Eisenbarth, “Sexual dimorphism in transmission of expression of islet autoantibodies to offspring,” Diabetologia, vol. 38, no. 11, pp. 1353–1357, 1995.
[60]
C. Wallace, D. J. Smyth, M. Maisuria-Armer, N. M. Walker, J. A. Todd, and D. G. Clayton, “The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes,” Nature Genetics, vol. 42, no. 1, pp. 68–71, 2010.
[61]
V. K. Rakyan, H. Beyan, T. A. Down et al., “Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis,” PLoS Genetics, vol. 7, no. 9, Article ID e1002300, 2011.
[62]
J. Nerup, P. Platz, O. O. Andersen et al., “HL A antigens and diabetes mellitus,” The Lancet, vol. 2, no. 7885, pp. 864–866, 1974.
[63]
G. I. Bell, S. Horita, and J. H. Karam, “A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus,” Diabetes, vol. 33, no. 2, pp. 176–183, 1984.
[64]
L. Nisticò, R. Buzzetti, L. E. Pritchard et al., “The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian diabetes registry,” Human Molecular Genetics, vol. 5, no. 7, pp. 1075–1080, 1996.
[65]
N. Bottini, L. Musumeci, A. Alonso et al., “A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes,” Nature Genetics, vol. 36, no. 4, pp. 337–338, 2004.
[66]
A. Vella, J. D. Cooper, C. E. Lowe et al., “Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms,” American Journal of Human Genetics, vol. 76, no. 5, pp. 773–779, 2005.
[67]
M. Bakay, R. Pandey, and H. Hakonarson, “Genes involved in type 1 diabetes: an update,” Genes, vol. 4, no. 4, pp. 499–521, 2013.
[68]
S. Nejentsev, N. Walker, D. Riches, M. Egholm, and J. A. Todd, “Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes,” Science, vol. 324, no. 5925, pp. 387–389, 2009.
[69]
M. Heinig, E. Petretto, C. Wallace, and S. A. Cook, “A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk,” Nature, vol. 467, no. 7314, pp. 460–464, 2010.
[70]
H. Hakonarson, S. F. A. Grant, J. P. Bradfield et al., “A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene,” Nature, vol. 448, no. 7153, pp. 591–594, 2007.
[71]
J. A. Todd, N. M. Walker, J. D. Cooper, et al., “Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes,” Nature Genetics, vol. 39, no. 7, pp. 857–864, 2007.
[72]
The Wellcome Trust Case Control Consortium, “Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls,” Nature, vol. 447, no. 7145, pp. 661–678, 2007.
[73]
J. D. Cooper, D. J. Smyth, A. M. Smiles et al., “Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci,” Nature Genetics, vol. 40, no. 12, pp. 1399–1401, 2008.
[74]
D. J. Smyth, V. Plagnol, N. M. Walker, et al., “Shared and distinct genetic variants in type 1 diabetes and celiac disease,” The New Englend Journal of Medicine, vol. 359, no. 26, pp. 2767–2777, 2008.
[75]
J. C. Barrett, D. G. Clayton, P. Concannon, et al., “Type 1 Diabetes Genetics Consortium. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes,” Nature Genetics, vol. 41, no. 6, pp. 703–707, 2009.
[76]
S. F. Grant, H. Q. Qu, J. P. Bradfield, et al., “Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes,” Diabetes, vol. 58, no. 1, pp. 290–295, 2009.
[77]
C. Wallace, D. J. Smyth, M. Maisuria-Armer, N. M. Walker, J. A. Todd, and D. G. Clayton, “The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes,” Nature Genetics, vol. 42, no. 1, pp. 68–71, 2010.
[78]
J. P. Bradfield, H. Q. Qu, and K. Wang, “A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci,” PLoS Genetics, vol. 7, no. 9, Article ID e1002293, 2011.
[79]
V. Plagnol, J. M. M. Howson, D. J. Smyth, et al., “Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases,” PLoS Genetics, vol. 7, no. 8, Article ID e1002216, 2006.
[80]
T. Bazzaz, M. M. Amoli, Z. Taheri, et al., “TNF-α and IFN-γ gene variation and genetic susceptibility to type 1 diabetes and its microangiopathic complications,” Journal of Diabetes and Metabolic Disorders, vol. 13, p. 46, 2014.
[81]
http://www.t1dbase.org/page/Regions.
[82]
W.-C. G. Yeung, W. D. Rawlinson, and M. E. Craig, “Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies,” British Medical Journal, vol. 342, no. 7794, article d35, 2011.
[83]
A. D. Paterson, “Genetic epidemiology of type 1 diabetes,” Current Diabetes Reports, vol. 6, no. 2, pp. 139–146, 2006.
[84]
Y.-H. Qiu, F.-Y. Deng, M.-J. Li, and S.-F. Lei, “Identification of novel risk genes associated with type 1 diabetes mellitus using a genome-wide gene-based association analysis,” Journal of Diabetes Investigation, 2014.
[85]
C. J. Fox and J. S. Danska, “Independent genetic regulation of T-cell and antigen-presenting cell participation in autoimmune islet inflammation,” Diabetes, vol. 47, no. 3, pp. 331–338, 1998.
[86]
P. L. Kendall, G. Yu, E. J. Woodward, and J. W. Thomas, “Tertiary lymphoid structures in the pancreas promote selection of B lymphocytes in autoimmune diabetes,” The Journal of Immunology, vol. 178, no. 9, pp. 5643–5651, 2007.
[87]
A. Willcox, S. J. Richardson, A. J. Bone, A. K. Foulis, and N. G. Morgan, “Analysis of islet inflammation in human type 1 diabetes,” Clinical and Experimental Immunology, vol. 155, no. 2, pp. 173–181, 2009.
[88]
T. Habib, A. Funk, M. Rieck et al., “Altered B cell homeostasis is associated with type I diabetes and carriers of the PTPN22 allelic variant,” The Journal of Immunology, vol. 188, no. 1, pp. 487–496, 2012.
[89]
W. S. Thompson, M. Pekalski, H. Z. Simons, et al., “Multi-parametric flow cytometric and genetic investigation of peripheral B-cell compartment in human type 1 diabetes,” Clinical and Experimental Immunology, vol. 177, no. 3, pp. 571–585, 2014.
[90]
M. Yang, K. Rui, S. Wang, and L. Lu, “Regulatory B cells in autoimmune diseases,” Cellular and Molecular Immunology, vol. 10, no. 2, pp. 122–132, 2013.
[91]
K. Schroder, P. J. Hertzog, T. Ravasi, and D. A. Hume, “Interferon-γ: an overview of signals, mechanisms and functions,” Journal of Leukocyte Biology, vol. 75, no. 2, pp. 163–189, 2004.
[92]
http://www.phgfoundation.org/news/4515.
[93]
C. Guiducci, M. Gong, Z. Xu et al., “TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus,” Nature, vol. 465, no. 7300, pp. 937–941, 2010.
[94]
A. Rabinovitch, “An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus,” Diabetes/Metabolism Reviews, vol. 14, no. 2, pp. 129–151, 1998.
[95]
A. K. Foulis, M. A. Farquharson, and A. Meager, “Immunoreactive α-interferon in insulin-secreting β cells in type 1 diabetes mellitus,” The Lancet, vol. 2, no. 8573, pp. 1423–1427, 1987.
[96]
G. C. Toms, P. Baker, and B. J. Boucher, “The production of immunoreactive α- and γ-interferon by circulating mononuclear cells in type 1 diabetes,” Diabetic Medicine, vol. 8, no. 6, pp. 547–550, 1991.
[97]
W. Chehadeh, J. Kerr-Conte, F. Pattou et al., “Persistent infection of human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesis in β cells,” Journal of Virology, vol. 74, no. 21, pp. 10153–10164, 2000.
[98]
X. Li, S. Leung, S. Qureshi, J. E. Darnell Jr., and G. R. Stark, “Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-α,” The Journal of Biological Chemistry, vol. 271, no. 10, pp. 5790–5794, 1996.
[99]
A. Takaoka, Y. Mitani, H. Suemori et al., “Cross talk between interferon-γ and -α/β signaling components in caveolar membrane domains,” Science, vol. 288, no. 5475, pp. 2357–2360, 2000.
[100]
M. Giroux, M. Schmidt, and A. Descoteaux, “IFN-γ-induced MHC class II expression: transactivation of class II transactivator promoter IV by IFN regulatory factor-1 is regulated by protein kinase C-α,” The Journal of Immunology, vol. 171, no. 8, pp. 4187–4194, 2003.
[101]
K. Lind, S. J. Richardson, P. Leete, N. G. Morgan, O. Korsgren, and M. Flodstr?m-Tullberga, “Induction of an antiviral state and attenuated coxsackievirus replication in type III interferon-treated primary human pancreatic islets,” Journal of Virology, vol. 87, no. 13, pp. 7646–7654, 2013.
[102]
C. Y. Pak, R. G. McArthur, H.-M. Eun, and J.-W. Yoon, “Association of cytomegalovirus infection with autoimmune type 1 diabetes,” The Lancet, vol. 332, no. 8601, pp. 1–4, 1988.
[103]
H. S. Hiemstra, N. C. Schloot, P. A. van Veelen et al., “Cytomegalovirus in autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 7, pp. 3988–3991, 2001.
[104]
M. Sester, U. Sester, B. C. G?rtner, M. Girndt, A. Meyerhans, and H. K?hler, “Dominance of virus-specific CD8 T cells in human primary cytomegalovirus infection,” Journal of the American Society of Nephrology, vol. 13, no. 10, pp. 2577–2584, 2002.
[105]
A. Kasuga, R. Harada, and T. Saruta, “Insulin-dependent diabetes mellitus associated with parvovirus B19 infection,” Annals of Internal Medicine, vol. 125, no. 8, pp. 700–701, 1996.
[106]
P. Vigeant, H. A. Menard, and G. Boire, “Chronic modulation of the autoimmune response following parvovirus B19 infection,” Journal of Rheumatology, vol. 21, no. 6, pp. 1165–1167, 1994.
[107]
M. C. Honeyman, N. L. Stone, B. A. Falk, G. Nepom, and L. C. Harrison, “Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens,” Journal of Immunology, vol. 184, no. 4, pp. 2204–2210, 2010.
[108]
F. Ginsberg-Fellner, M. E. Witt, S. Yagihashi et al., “Congenital rubella syndrome as a model for Type 1 (insulin-dependent) diabetes mellitus: increased prevalence of islet cell surface antibodies,” Diabetologia, vol. 27, no. 1, pp. 87–89, 1984.
[109]
D. Ou, L. A. Mitchell, D. L. Metzger, S. Gillam, and A. J. Tingle, “Cross-reactive rubella virus and glutamic acid decarboxylase (65 and 67) protein determinants recognised by T cells of patients with type I diabetes mellitus,” Diabetologia, vol. 43, no. 6, pp. 750–762, 2000.
[110]
M. G. Cavallo, M. G. Baroni, A. Toto et al., “Viral infection induces cytokine release by beta islet cells,” Immunology, vol. 75, no. 4, pp. 664–668, 1992.
[111]
H. Hyoty, P. Parkkonen, M. Rode, O. Bakke, and P. Leinikki, “Common peptide epitope in mumps virus nucleocapsid protein and MHC class II-associated invariant chain,” Scandinavian Journal of Immunology, vol. 37, no. 5, pp. 550–558, 1993.
[112]
B. Conrad, R. N. Weissmahr, J. B?ni, R. Arcari, J. Schüpbach, and B. Mach, “A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes,” Cell, vol. 90, no. 2, pp. 303–313, 1997.
[113]
G. Tapia, O. Cinek, T. Rasmussen, B. Grinde, L. C. Stene, and K. S. R?nningen, “Longitudinal study of parechovirus infection in infancy and risk of repeated positivity for multiple islet autoantibodies: the MIDIA study,” Pediatric Diabetes, vol. 12, no. 1, pp. 58–62, 2011.
[114]
G. R. Vreugdenhil, N. C. Schloot, A. Hoorens et al., “Acute onset of type I diabetes mellitus after severe echovirus 9 infection: putative pathogenic pathways,” Clinical Infectious Diseases, vol. 31, no. 4, pp. 1025–1031, 2000.
[115]
J. W. Yoon, T. Onodera, and A. L. Notkins, “Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4,” The Journal of Experimental Medicine, vol. 148, no. 4, pp. 1068–1080, 1978.
[116]
M. Lonnrot, K. Salminen, and M. Knip, “Enterovirus RNA in serum is a risk factor for beta-cell autoimmunity and clinical type 1 diabetes: a prospective study. Childhood Diabetes in Finland (DiMe) Study Group,” Journal of Medical Virology, vol. 61, no. 2, pp. 214–220, 2000.
[117]
D. V. Serreze, E. W. Ottendorfer, T. M. Elliss, C. J. Gauntt, and M. A. Atkinson, “Acceleration of type 1 diabetes by a coxsackievirus infection requires a preexisting critical mass of autoreactive T-cells in pancreatic islets,” Diabetes, vol. 49, no. 5, pp. 708–711, 2000.
[118]
M. S. Horwitz, L. M. Bradley, J. Harbertson, T. Krahl, J. Lee, and N. Sarvetnick, “Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry,” Nature Medicine, vol. 4, no. 7, pp. 781–785, 1998.
[119]
A. Willcox, S. J. Richardson, A. J. Bone, A. K. Foulis, and N. G. Morgan, “Immunohistochemical analysis of the relationship between islet cell proliferation and the production of the enteroviral capsid protein, VP1, in the islets of patients with recent-onset type 1 diabetes,” Diabetologia, vol. 54, no. 9, pp. 2417–2420, 2011.
[120]
B. M. Schulte, M. Kramer, M. Ansems et al., “Phagocytosis of enterovirus-infected pancreatic β-cells triggers innate immune responses in human dendritic cells,” Diabetes, vol. 59, no. 5, pp. 1182–1191, 2010.
[121]
F. Brilot, V. Geenen, D. Hober, and C. A. Stoddart, “Coxsackievirus B4 infection of human fetal thymus cells,” Journal of Virology, vol. 78, no. 18, pp. 9854–9861, 2004.
[122]
M. Oikarinen, S. Tauriainen, T. Honkanen et al., “Detection of enteroviruses in the intestine of type 1 diabetic patients,” Clinical and Experimental Immunology, vol. 151, no. 1, pp. 71–75, 2008.
[123]
I. S. Yap, G. Giddings, E. Pocock, and J. K. Chantler, “Lack of islet neogenesis plays a key role in beta-cell depletion in mice infected with a diabetogenic variant of coxsackievirus B4,” Journal of General Virology, vol. 84, no. 11, pp. 3051–3068, 2003.
[124]
K. P. Ward, W. H. Galloway, and I. A. Auchterlonie, “Congenital cytomegalovirus infection and diabetes,” The Lancet, vol. 1, no. 8114, article 497, 1979.
[125]
C. Y. Pak, C. Y. Cha, R. V. Rajotte, R. G. McArthur, and J. W. Yoon, “Human pancreatic islet cell specific 38 kilodalton autoantigen identified by cytomegalovirus-induced monoclonal islet cell autoantibody,” Diabetologia, vol. 33, no. 9, pp. 569–572, 1990.
[126]
K. Numazaki, H. Goldman, I. Wong, and M. A. Wainberg, “Viral infection of human fetal islets of Langerhans. Replication of human cytomegalovirus in cultured human fetal pancreatic islets,” American Journal of Clinical Pathology, vol. 90, no. 1, pp. 52–57, 1988.
[127]
M. J. Smelt, M. M. Faas, B. J. de Haan, et al., “Rat pancreatic beta cells and cytomegalovirus infection,” Pancreas, vol. 39, no. 1, pp. 47–56, 2010.
[128]
J. Aarnisalo, R. Veijola, R. Vainionp??, O. Simell, M. Knip, and J. Ilonen, “Cytomegalovirus infection in early infancy: risk of induction and progression of autoimmunity associated with type 1 diabetes,” Diabetologia, vol. 51, no. 5, pp. 769–772, 2008.
[129]
S.-A. Ivarsson, B. Lindberg, K. O. Nilsson, K. Ahlfors, and L. Svanberg, “The prevalence of type 1 diabetes mellitus at follow-up of Swedish infants congenitally infected with cytomegalovirus,” Diabetic Medicine, vol. 10, no. 6, pp. 521–523, 1993.
[130]
A. K. Foulis, M. McGill, M. A. Farquharson, and D. A. Hilton, “A search for evidence of viral infection in pancreases of newly diagnosed patients with IDDM,” Diabetologia, vol. 40, no. 1, pp. 53–61, 1997.
[131]
N. Itoh, T. Hanafusa, K. Yamagata et al., “No detectable cytomegalovirus and Epstein-Barr virus genomes in the pancreas of recent-onset IDDM patients,” Diabetologia, vol. 38, no. 6, pp. 667–671, 1995.
[132]
Y. Munakata, T. Kodera, T. Saito, and T. Sasaki, “Rheumatoid arthritis, type 1 diabetes, and Graves' disease after acute parvovirus B19 infection,” The Lancet, vol. 366, no. 9487, article 780, 2005.
[133]
A. von Poblotzki, C. Gerdes, U. Reischl, H. Wolf, and S. Modrow, “Lymphoproliferative responses after infection with human parvovirus B19,” Journal of Virology, vol. 70, no. 10, pp. 7327–7330, 1996.
[134]
D. Zipris, J.-L. Hillebrands, R. M. Welsh et al., “Infections that induce autoimmune diabetes in BBDR rats modulate CD4+CD25+ T cell populations,” The Journal of Immunology, vol. 170, no. 7, pp. 3592–3602, 2003.
[135]
D. Zipris, E. Lien, J. X. Xie, D. L. Greiner, J. P. Mordes, and A. A. Rossini, “TLR activation synergizes with Kilham rat virus infection to induce diabetes in BBDR rats,” The Journal of Immunology, vol. 174, no. 1, pp. 131–142, 2005.
[136]
M. C. Honeyman, B. S. Coulson, N. L. Stone et al., “Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes,” Diabetes, vol. 49, no. 8, pp. 1319–1324, 2000.
[137]
K. L. Graham, N. Sanders, Y. Tan, J. Allison, T. W. H. Kay, and B. S. Coulson, “Rotavirus infection accelerates type 1 diabetes in mice with established insulitis,” Journal of Virology, vol. 82, no. 13, pp. 6139–6149, 2008.
[138]
J. A. Pane, N. L. Webster, and B. S. Coulson, “Rotavirus activates lymphocytes from non-obese diabetic mice by triggering toll-like receptor 7 signaling and interferon production in plasmacytoid dendritic cells,” PLoS Pathogens, vol. 10, no. 3, Article ID e1003998, 2014.
[139]
E. A. M. Gale, “Congenital rubella: citation virus or viral cause of type 1 diabetes?” Diabetologia, vol. 51, no. 9, pp. 1559–1566, 2008.
[140]
B. Lindberg, K. Ahlfors, A. Carlsson et al., “Previous exposure to measles, mumps, and rubella—but not vaccination during adolescence—correlates to the prevalence of pancreatic and thyroid autoantibodies,” Pediatrics, vol. 104, no. 1, article e12, 1999.
[141]
F. Ramondetti, S. Sacco, M. Comelli, et al., “Type 1 diabetes and measles, mumps and rubella chilhood infections within the Italian Insulin dependent diabetes regitstry,” Diabetic Medicine, vol. 29, no. 6, pp. 761–766, 2011.
[142]
P. Parkkonen, H. Hyoty, L. Koskinen, and P. Leinikki, “Mumps virus infects Beta cells in human fetal islet cell cultures upregulating the expression of HLA class I molecules,” Diabetologia, vol. 35, no. 1, pp. 63–69, 1992.
[143]
K. Helmke, A. Otten, and W. Willems, “Islet cell antibodies in children with mumps infection,” The Lancet, vol. 2, no. 8187, pp. 211–212, 1980.
[144]
H. Hyoty, M. Hiltunen, A. Reunanen et al., “Decline of mumps antibodies in type 1 (insulin-dependent) diabetic children and a plateau in the rising incidence of type 1 diabetes after introduction of the mumps-measles-rubella vaccine in Finland,” Diabetologia, vol. 36, no. 12, pp. 1303–1308, 1993.
[145]
R. L?wer, J. L?wer, and R. Kurth, “The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 11, pp. 5177–5184, 1996.
[146]
E. Balada, M. Vilardell-Tarrés, and J. Ordi-Ros, “Implication of human endogenous retroviruses in the development of autoimmune diseases,” International Reviews of Immunology, vol. 29, no. 4, pp. 351–370, 2010.
[147]
M. S. Oberste, E. Gotuzzo, P. Blair et al., “Human febrile illness caused by encephalomyocarditis virus infection, peru,” Emerging Infectious Diseases, vol. 15, no. 4, pp. 640–646, 2009.
[148]
S. Nagafuchi, M. Teshima, Y. Kai, et al., “The significance of tyrosine kinase 2 gene in encephalomyocarditis-D virus-induced diabetes as studied in Tyk2 gene knockout mice (P6334),” Journal of Immunology, vol. 190, pp. 182–119, 2013, (Meeting Abstract Supplement).
[149]
B. Niklasson, K. E. Heller, B. Sch?necker et al., “Development of type 1 diabetes in wild bank voles associated with islet autoantibodies the novel Ljungan virus,” Experimental Diabesity Research, vol. 4, no. 1, pp. 35–44, 2003.
[150]
M. Roivainen, P. Ylipaasto, C. Savolainen, J. Galama, T. Hovi, and T. Otonkoski, “Functional impairment and killing of human beta cells by enteroviruses: the capacity is shared by a wide range of serotypes, but the extent is a characteristic of individual virus strains,” Diabetologia, vol. 45, no. 5, pp. 693–702, 2002.
[151]
E. Cabrera-Rode, L. Sarmiento, C. Tiberti et al., “Type 1 diabetes islet associated antibodies in subjects infected by echovirus 16,” Diabetologia, vol. 46, no. 10, pp. 1348–1353, 2003.
[152]
E. Cabrera-Rode, L. Sarmiento, G. Molina et al., “Islet cell related antibodies and type 1 diabetes associated with echovirus 30 epidemic: a case report,” Journal of Medical Virology, vol. 76, no. 3, pp. 373–377, 2005.
[153]
O. Diaz-Horta, L. Sarmiento, A. Baj, E. Cabrera-Rode, and A. Toniolo, “Echovirus epidemics, autoimmunity, and type 1 diabetes,” in Type 1 Diabetes - Pathogenesis, Genetics and Immunotherapy, D. Wagner, Ed., pp. 211–230, InTech, 2011, http://www.intechopen.com/books/type-1-diabetes-pathogenesis-genetics-and-immunotherapy/echovirus-epidemics-autoimmunity-and-type-1-diabetes.
[154]
H. Hyoty and K. W. Taylor, “The role of viruses in human diabetes,” Diabetologia, vol. 45, no. 10, pp. 1353–1361, 2002.
[155]
T. Otonkoski, M. Roivainen, O. Vaarala et al., “Neonatal Type I diabetes associated with maternal echovirus 6 infection: a case report,” Diabetologia, vol. 43, no. 10, pp. 1235–1238, 2000.
[156]
?. H. Williams, S. Oikarinen, S. Tauriainen, K. Salminen, H. Hy?ty, and G. Stanway, “Molecular analysis of an echovirus 3 strain isolated from an individual concurrently with appearance of islet cell and IA-2 autoantibodies,” Journal of Clinical Microbiology, vol. 44, no. 2, pp. 441–448, 2006.
[157]
M. L. Sussman, L. Strauss, and H. L. Hodes, “Fatal coxsackie group B virus infection in the newborn; report of a case with necropsy findings and brief review of the literature,” American Journal of Diseases of Children, vol. 97, no. 4, pp. 483–492, 1959.
[158]
D. R. Gamble, M. L. Kinsley, M. G. FitzGerald, R. Bolton, and K. W. Taylor, “Viral antibodies in diabetes mellitus,” British Medical Journal, vol. 3, no. 671, pp. 627–630, 1969.
[159]
L. Andreoletti, D. Hober, C. Hober-Vandenberghe, et al., “Detection of coxsackie B virus RNA sequences in whole blood samples from adult patients at the onset of type I diabetes mellitus,” Journal of Medical Virology, vol. 52, no. 2, pp. 121–127, 1997.
[160]
K. Sadeharju, A.-M. H?m?l?inen, M. Knip et al., “Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial,” Clinical and Experimental Immunology, vol. 132, no. 2, pp. 271–277, 2003.
[161]
S. Tauriainen, S. Oikarinen, M. Oikarinen, and H. Hy?ty, “Enteroviruses in the pathogenesis of type 1 diabetes,” Seminars in Immunopathology, vol. 33, no. 1, pp. 45–55, 2011.
[162]
L. Sarmiento, E. Cabrera-Rode, L. Lekuleni et al., “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, vol. 40, no. 7, pp. 540–545, 2007.
[163]
M. Karvonen, M. Viik-Kajander, E. Moltchanova, I. Libman, R. LaPorte, and J. Tuomilehto, “Incidence of childhood type 1 diabetes worldwide,” Diabetes Care, vol. 23, no. 10, pp. 1516–1526, 2000.
[164]
J. W. Yoon, M. Austin, T. Onodera, and A. L. Notkins, “Virus-induced diabetes mellitus. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis,” The New England Journal of Medicine, vol. 300, no. 21, pp. 1173–1179, 1979.
[165]
K. M. Drescher, K. Kono, S. Bopegamage, S. D. Carson, and S. Tracy, “Coxsackievirus B3 infection and type 1 diabetes development in NOD mice: Insulitis determines susceptibility of pancreatic islets to virus infection,” Virology, vol. 329, no. 2, pp. 381–394, 2004.
[166]
T. Kanno, K. Kim, K. Kono, K. M. Drescher, N. M. Chapman, and S. Tracy, “Group B coxsackievirus diabetogenic phenotype correlates with viral replication efficiency,” Journal of Virology, vol. 80, no. 11, pp. 5637–5643, 2006.
[167]
S. Tracy, K. M. Drescher, N. M. Chapman et al., “Toward testing the hypothesis that group B coxsackieviruses (CVB) trigger insulin-dependent diabetes: inoculating nonobese diabetic mice with CVB markedly lowers diabetes incidence,” Journal of Virology, vol. 76, no. 23, pp. 12097–12111, 2002.
[168]
S. Oikarinen, S. Tauriainen, D. Hober et al., “Virus antibody survey in different european populations indicates risk association between coxsackievirus B1 and type 1 diabetes,” Diabetes, vol. 63, no. 2, pp. 655–662, 2014.
[169]
O. H. Laitinen, H. Honkanen, O. Pakkanen et al., “Coxsackievirus B1 is associated with induction of β-cells autoimmunity that portends type 1 diabetes,” Diabetes, vol. 63, no. 2, pp. 446–455, 2014.
[170]
S. Bopegamage, J. Precechtelova, L. Marosova, et al., “Outcome of challenge with coxsackievirus B4 in young mice after maternal infection with the same virus during gestation,” FEMS Immunology & Medical Microbiology, vol. 64, no. 2, pp. 184–190, 2012.
[171]
P. G. Larsson, T. Lakshmikanth, E. Svedin, C. King, and M. Flodstr?m-Tullberg, “Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice,” Diabetologia, vol. 56, no. 4, pp. 867–874, 2013.
[172]
G. Frisk and H. Diderholm, “Tissue culture of isolated human pancreatic islets infected with different strains of Coxsackievirus B4: assessment of virus replication and effects on islet morphology and insulin release,” Experimental Diabesity Research, vol. 1, no. 3, pp. 165–175, 2000.
[173]
M. Roivainen, S. Rasilainen, P. Ylipaasto et al., “Mechanisms of coxsackievirus-induced damage to human pancreatic β-cells,” The Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 1, pp. 432–440, 2000.
[174]
S. A. Bopegamage and A. Petrovicova, “In vitro infection of mouse pancreatic islet cells with coxsackie viruses,” Acta Virologica, vol. 38, no. 5, pp. 251–255, 1994.
[175]
H. Yin, A.-K. Berg, J. Westman, C. Hellerstr?m, and G. Frisk, “Complete nucleotide sequence of a coxsackievirus B-4 strain capable of establishing persistent infection in human pancreatic islet cells: effects on insulin release, proinsulin synthesis, and cell morphology,” Journal of Medical Virology, vol. 68, no. 4, pp. 544–557, 2002.
[176]
M. Roivainen, P. Ylipaasto, J. Ustinov, T. Hovi, and T. Otonkoshi, “Screening enteroviruses for β-cell tropism using foetal porcine β-cells,” Journal of General Virology, vol. 82, no. 8, pp. 1909–1916, 2001.
[177]
T. M. Szopa, D. R. Gamble, and K. W. Taylor, “Biochemical changes induced by Coxsackie B4 virus in short-term culture of mouse pancreatic islets,” Bioscience Reports, vol. 5, no. 1, pp. 63–69, 1985.
[178]
N. Welsh, B. Margulis, L. A. Borg et al., “Differences in the expression of heat-shock proteins and antioxidant enzymes between human and rodent pancreatic islets: implications for the pathogenesis of insulin-dependent diabetes mellitus,” Molecular Medicine, vol. 1, no. 7, pp. 806–820, 1995.
[179]
G. G. Dahlquist, J. E. Boman, and P. Juto, “Enteroviral RNA and IgM antibodies in early pregnancy and risk for childhood-onset IDDM in offspring,” Diabetes Care, vol. 22, no. 2, pp. 364–365, 1999.
[180]
M. Elfving, J. Svensson, S. Oikarinen et al., “Maternal enterovirus infection during pregnancy as a risk factor in offspring diagnosed with type 1 diabetes between 15 and 30 years of age,” Experimental diabetes research, vol. 2008, pp. 271958–271964, 2008.
[181]
H. Viskari, J. Ludvigsson, R. Uibo et al., “Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies: time trends and geographical variation,” Diabetologia, vol. 48, no. 7, pp. 1280–1287, 2005.
[182]
H. R. Viskari, M. Roivainen, A. Reunanen et al., “Maternal first-trimester enterovirus infection and future risk of type 1 diabetes in the exposed fetus,” Diabetes, vol. 51, no. 8, pp. 2568–2571, 2002.
[183]
R. Coutant, J. C. Carel, P. Lebon, L. Cantero-Aguilar, P. Lebon, and P. F. Bougnères, “Detection of enterovirus RNA sequences in serum samples from autoantibody-positive subjects at risk for diabetes,” Diabetic Medicine, vol. 19, no. 11, pp. 968–969, 2002.
[184]
G. Frisk and H. Diderholm, “Antibody responses to different strains of Coxsackie B4 virus in patients with newly diagnosed type I diabetes mellitus or aseptic meningitis,” Journal of Infection, vol. 34, no. 3, pp. 205–210, 1997.
[185]
G. Frisk and T. Tuvemo, “Enterovirus infections with β-cell tropic strains are frequent in siblings of children diagnosed with type 1 diabetes children and in association with elevated levels of GAD65 antibodies,” Journal of Medical Virology, vol. 73, no. 3, pp. 450–459, 2004.
[186]
M. M. Maha, M. A. Ali, S. E. Abdel-Rehim, E. A. Abu-Shady, B. M. El-Naggar, and Y. Z. Maha, “The role of coxsackieviruses infection in the children of insulin dependent diabetes mellitus.,” The Journal of the Egyptian Public Health Association, vol. 78, no. 3-4, pp. 305–318, 2003.
[187]
R. Varela-Calvino, R. Ellis, G. Sgarbi, C. M. Dayan, and M. Peakman, “Characterization of the T-cell response to coxsackievirus B4: evidence that effector memory cells predominate in patients with type 1 diabetes,” Diabetes, vol. 51, no. 6, pp. 1745–1753, 2002.
[188]
L. C. Stene, S. Oikarinen, H. Hy?ty et al., “Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY),” Diabetes, vol. 59, no. 12, pp. 3174–3180, 2010.
[189]
S. Oikarinen, M. Martiskainen, S. Tauriainen et al., “Enterovirus RNA in blood is linked to the development of type 1 diabetes,” Diabetes, vol. 60, no. 1, pp. 276–279, 2011.
[190]
K. K. Salminen, T. Vuorinen, S. Oikarinen et al., “Isolation of enterovirus strains from children with preclinical Type 1 diabetes,” Diabetic Medicine, vol. 21, no. 2, pp. 156–164, 2004.
[191]
G. G. Dahlquist, J. Forsberg, L. Hagenfeldt, J. Boman, and P. Juto, “Increased prevalence of enteroviral RNA in blood spots from newborn children who later developed type 1 diabetes: a population-based case-control study,” Diabetes Care, vol. 27, no. 1, pp. 285–286, 2004.
[192]
G. B. Clements, D. N. Galbraith, and K. W. Taylor, “Coxsackie B virus infection and onset of childhood diabetes,” The Lancet, vol. 346, no. 8969, pp. 221–223, 1995.
[193]
M. E. Craig, N. J. Howard, M. Silink, and W. D. Rawlinson, “Reduced frequency of HLA DRB1-03, DQB1-02 in children with type 1 diabetes associated with enterovirus RNA,” Journal of Infectious Diseases, vol. 187, no. 10, pp. 1562–1570, 2003.
[194]
H. Kawashima, T. Ihara, H. Ioi et al., “Enterovirus-related type 1 diabetes mellitus and antibodies to glutamic acid decarboxylase in Japan,” Journal of Infection, vol. 49, no. 2, pp. 147–151, 2004.
[195]
C. Nairn, D. N. Galbraith, K. W. Taylor, and G. B. Clements, “Enterovirus variants in the serum of children at the onset oftype 1 diabetes mellitus,” Diabetic Medicine, vol. 16, no. 6, pp. 509–513, 1999.
[196]
H. Yin, A.-K. Berg, T. Tuvemo, and G. Frisk, “Enterovirus RNA is found in peripheral blood mononuclear cells in a majority of type 1 diabetic children at onset,” Diabetes, vol. 51, no. 6, pp. 1964–1971, 2002.
[197]
A. Toniolo, G. Maccari, G. Federico, et al., “Are enterovirus infections linked to the early stages of type 1 diabetes?” in Proceedings of the American Society for Microbiology Meeting, CA. Abst. ST-902, San Diego, Calif, USA, 2010.
[198]
B. M. Schulte, J. Bakkers, K. H. W. Lanke et al., “Detection of enterovirus RNA in peripheral blood mononuclear cells of type 1 diabetic patients beyond the stage of acute infection,” Viral Immunology, vol. 23, no. 1, pp. 99–104, 2010.
[199]
H. Champsaur, E. Dussaix, D. Samolyk, M. Fabre, C. Bach, and R. Assan, “Diabetes and Coxsackie virus B5 infection,” The Lancet, vol. 315, no. 8162, p. 251, 1980.
[200]
C. di Pietro, M. J. del Guercio, G. P. Paolino, M. Barbi, P. Ferrante, and G. Chiumello, “Type 1 diabetes and Coxsackie virus infection,” Helvetica Paediatrica Acta, vol. 34, no. 6, pp. 557–561, 1979.
[201]
P. Ylipaasto, K. Klingel, A. M. Lindberg et al., “Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells,” Diabetologia, vol. 47, no. 2, pp. 225–239, 2004.
[202]
F. Dotta, S. Censini, A. G. S. van Halteren et al., “Coxsackie B4 virus infection of β cells and natural killer cell insulitis in recent-onset type 1 diabetic patients,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 12, pp. 5115–5120, 2007.
[203]
M. Oikarinen, S. Tauriainen, T. Honkanen et al., “Analysis of pancreas tissue in a child positive for islet cell antibodies,” Diabetologia, vol. 51, no. 10, pp. 1796–1802, 2008.
[204]
S. J. Richardson, A. Willcox, A. J. Bone, A. K. Foulis, and N. G. Morgan, “The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes,” Diabetologia, vol. 52, no. 6, pp. 1143–1151, 2009.
[205]
P. Ylipaasto, B. Kutlu, S. Rasilainen et al., “Global profiling of coxsackievirus- and cytokine-induced gene expression in human pancreatic islets,” Diabetologia, vol. 48, no. 8, pp. 1510–1522, 2005.
[206]
D. P. Strachan, “Hay fever, hygiene, and household size,” British Medical Journal, vol. 299, no. 6710, pp. 1259–1260, 1989.
[207]
J. F. Bach, “The effect of infections on susceptibility to autoimmune and allergic diseases,” The New England Journal of Medicine, vol. 347, no. 12, pp. 911–920, 2002.
[208]
H. S. Lee, T. Briese, C. Winkler et al., “Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes,” Diabetologia, vol. 56, no. 8, pp. 1705–1711, 2013.
[209]
T. Boettler and M. Von Herrath, “Protection against or triggering of Type 1 diabetes? Different roles for viral infections,” Expert Review of Clinical Immunology, vol. 7, no. 1, pp. 45–53, 2011.
[210]
N. M. Chapman, K. Coppieters, M. von Herrath, and S. Tracy, “The microbiology of human hygiene and its impact on type 1 diabetes,” Islets, vol. 4, no. 4, pp. 253–261, 2012.
[211]
K. M. Drescher and S. Tracy, “The CVB and etiology of type 1 diabetes,” Current Topics in Microbiology and Immunology, vol. 323, pp. 259–274, 2008.
[212]
H. Al-Hello, B. Davydova, T. Smura et al., “Phenotypic and genetic changes in coxsackievirus B5 following repeated passage in mouse pancreas in vivo,” Journal of Medical Virology, vol. 75, no. 4, pp. 566–574, 2005.
[213]
M. Flodstr?m, A. Maday, D. Balakrishna, M. M. Cleary, A. Yoshimura, and N. Sarvetnick, “Target cell defense prevents the development of diabetes after viral infection,” Nature Immunology, vol. 3, no. 4, pp. 373–382, 2002.
[214]
G. Frisk, K. Jansson, M. Ericsson, and H. Diderholm, “Differences in inhibition of replication between Coxsackie B4 virus strains in various cell lines by antibodies to some cell surface proteins,” Virus Research, vol. 73, no. 2, pp. 121–130, 2001.
[215]
T. M. Szopa, P. A. Titchener, N. D. Portwood, and K. W. Taylor, “Diabetes mellitus due to viruse—some recent developments,” Diabetologia, vol. 36, no. 8, pp. 687–695, 1993.
[216]
E. Jaeckel, M. Manns, and M. von Herrath, “Viruses and diabetes,” Annals of the New York Academy of Sciences, vol. 958, pp. 7–25, 2002.
[217]
S. Skarsvik, J. Puranen, J. Honkanen, et al., “Decreased in vitro type 1 immune response against coxsackie virus B4 in children with type 1 diabetes,” Diabetes, vol. 55, no. 4, pp. 996–1003, 2006.
[218]
K. Klingel, S. Stephan, M. Sauter et al., “Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets,” Journal of Virology, vol. 70, no. 12, pp. 8888–8895, 1996.
[219]
B. O. Roep, H. S. Hiemstra, N. C. Schloot et al., “Molecular mimicry in type 1 diabetes: immune cross-reactivity between islet autoantigen and human cytomegalovirus but not Coxsackie virus,” Annals of the New York Academy of Sciences, vol. 958, pp. 163–165, 2002.
[220]
M. A. Atkinson, M. A. Bowman, L. Campbell, B. L. Darrow, D. L. Kaufman, and N. K. Maclaren, “Cellular immunity to a determinant common to glutamate decarboxylase and Coxsackie virus in insulin-dependent diabetes,” The Journal of Clinical Investigation, vol. 94, no. 5, pp. 2125–2129, 1994.
[221]
W. Richter, T. Mertens, B. Schoel et al., “Sequence homology of the diabetes-associated autoantigen glutamate decarboxylase with coxsackie B4-2C protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies,” Journal of Experimental Medicine, vol. 180, no. 2, pp. 721–726, 1994.
[222]
N. C. Schloot, S. J. M. Willemen, G. Duinkerken, J. W. Drijfhout, R. R. P. de Vries, and B. O. Roep, “Molecular mimicry in type 1 diabetes mellitus revisited: T-cell clones to GAD65 peptides with sequence homology to coxsackie or proinsulin peptides do not crossreact with homologous counterpart,” Human Immunology, vol. 62, no. 4, pp. 299–309, 2001.
[223]
R. S. Fujinami, M. G. von Herrath, U. Christen, and J. L. Whitton, “Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease,” Clinical Microbiology Reviews, vol. 19, no. 1, pp. 80–94, 2006.
[224]
M. S. Horwitz, A. Ilic, C. Fine, E. Rodriguez, and N. Sarvetnick, “Presented antigen from damaged pancreatic β cells activates autoreactive T cells in virus-mediated autoimmune diabetes,” Journal of Clinical Investigation, vol. 109, no. 1, pp. 79–87, 2002.
[225]
G. R. Vreugdenhil, P. G. Wijnands, M. G. Netea, J. W. M. van der Meer, W. J. G. Melchers, and J. M. D. Galama, “Enterovirus-induced production of pro-inflammatory and T-helper cytokines by human leukocytes,” Cytokine, vol. 12, no. 12, pp. 1793–1796, 2000.
[226]
G. R. Vreugdenhil, P. G. Wijnands, M. G. Netea, et al., “Coxsackie B virus induces TNF-α production in human pancreatic ductal cells,” in Enterovirus and Type 1 Diabetes Mellitus: Putative Pathogenic Pathways, G. R. Vreugdenhil, Ed., dissertation thesis, Print Panters Iskamp, Enschede, The Netherlands, 2001.
[227]
M. S. Horwitz, A. Ilic, C. Fine, B. Balasa, and N. Sarvetnick, “Coxsackieviral-mediated diabetes: induction requires antigen-presenting cells and is accompanied by phagocytosis of beta cells,” Clinical Immunology, vol. 110, no. 2, pp. 134–144, 2004.
[228]
M. S. Horwitz, C. Fine, A. Ilic, and N. Sarvetnick, “Requirements for viral-mediated autoimmune diabetes: β-cell damage and immune infiltration,” Journal of Autoimmunity, vol. 16, no. 3, pp. 211–217, 2001.
[229]
D. Hober, W. Chehadeh, J. Weill et al., “Circulating and cell-bound antibodies increase coxsackievirus B4-induced production of IFN-α by peripheral blood mononuclear cells from patients with type 1 diabetes,” Journal of General Virology, vol. 83, no. 9, pp. 2169–2176, 2002.
[230]
W. Chehadeh, A. Bouzidi, G. Alm, P. Wattré, and D. Hober, “Human antibodies isolated from plasma by affinity chromatography increase the coxsackievirus B4-induced synthesis of interferon-α by human peripheral blood mononuclear cells in vitro,” Journal of General Virology, vol. 82, no. 8, pp. 1899–1907, 2001.
[231]
D. Hober, W. Chehadeh, A. Bouzidi, and P. Wattré, “Antibody-dependent enhancement of Coxsackievirus B4 infectivity of human peripheral blood mononuclear cells results in increased interferon-α synthesis,” Journal of Infectious Diseases, vol. 184, no. 9, pp. 1098–1108, 2001.
[232]
P. Sauter, P.-E. Lobert, B. Lucas et al., “Role of the capsid protein VP4 in the plasma-dependent enhancement of the Coxsackievirus B4E2-infection of human peripheral blood cells,” Virus Research, vol. 125, no. 2, pp. 183–190, 2007.
[233]
P. Sauter, W. Chehadeh, P.-E. Lobert et al., “A part of the VP4 capsid protein exhibited by coxsackievirus B4 E2 is the target of antibodies contained in plasma from patients with type 1 diabetes,” Journal of Medical Virology, vol. 80, no. 5, pp. 866–878, 2008.
[234]
J. G. Rosmalen, W. van Ewijk, and P. J. Leenen, “T-cell education in autoimmune diabetes: teachers and students,” Trends in Immunology, vol. 23, no. 1, pp. 40–46, 2002.
[235]
F. Brilot, H. Jaidane, V. Geenen, and D. Hober, “Coxsackievirus B4 infection of murine foetal thymus organ cultures,” Journal of Medical Virology, vol. 80, no. 4, pp. 659–666, 2008.
[236]
H. Ja?dane, J. Gharbi, P.-E. Lobert et al., “Prolonged viral RNA detection in blood and lymphoid tissues from Coxsackievirus B4 E2 orally-inoculated Swiss mice,” Microbiology and Immunology, vol. 50, no. 12, pp. 971–974, 2006.
[237]
H. Ja?dane, P. Sauter, F. Sane, A. Goffard, J. Gharbi, and D. Hober, “Enteroviruses and type 1 diabetes: towards a better understanding of the relationship,” Reviews in Medical Virology, vol. 20, no. 5, pp. 265–280, 2010.
[238]
O. Vaarala, “Leaking gut in type 1 diabetes,” Current Opinion in Gastroenterolgy, vol. 24, no. 6, pp. 701–706, 2008.
[239]
X. Xu, J. D'Hoker, G. Stangé et al., “ cells can be generated from endogenous progenitors in injured adult mouse pancreas,” Cell, vol. 132, no. 2, pp. 197–207, 2008.
[240]
S. Bonner-Weir, “β-cell turnover: its assessment and implications,” Diabetes, vol. 50, no. 1, pp. S20–S24, 2001.
[241]
M. Almgren, T. Schlinzig, D. Gomez-Cabrero, et al., “Cesarean delivery and hematopoietic stem cell epigenetics in the newborn infant: implications for future health?” The American Journal of Obstetric and Gynecology, vol. 211, no. 5, pp. 502.e1–502.e8, 2014.