Viral infections in type 1 diabetes mellitus — why the β cells?
Open accessAbstract
Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection--particularly by enteroviruses (for example, coxsackievirus)--as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review.
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Increasing evidence supports viral infections as triggers of autoimmune diseases in general; type 1 diabetes mellitus has been linked to enterovirus infections and multiple sclerosis to Epstein-Barr virus infections.
“For example, type 1 diabetes mellitus was linked to enterovirus infections185 and multiple sclerosis to Epstein–Barr virus (EBV) infections186.”
From COVID-19 and cellular senescence (2023) · cites this paper as [185]
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Hay fever, hygiene, and household size.
Strachan, D. P. (1989) · BMJ · doi:10.1136/bmj.299.6710.1259 · Cited by 5,054 · see citing works
Atkinson, M. A., Eisenbarth, G. S., & Michels, A. W. (2014) · The Lancet · doi:10.1016/s0140-6736(13)60591-7 · Cited by 2,713 · see citing works
Genetic and epigenetic fine mapping of causal autoimmune disease variants
Farh, K. K.-H., Marson, A., Zhu, J., Kleinewietfeld, M., Housley, W. J., Beik, S., Shoresh, N., Whitton, H., Ryan, R. J. H., Shishkin, A. A., et al. (2015) · Nature · doi:10.1038/nature13835 · Cited by 1,956 · see citing works
Patterson, C. C., Dahlquist, G. G., Gyürüs, E., Green, A., & Soltész, G. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60568-7 · Cited by 1,854 · see citing works
Pathologic anatomy of the pancreas in juvenile diabetes mellitus
Gepts, W. (1965) · Diabetes · doi:10.2337/diab.14.10.619 · Cited by 1,345 · see citing works
Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children
Ziegler, A. G., Rewers, M., Simell, O., Simell, T., Lempainen, J., Steck, A., Winkler, C., Ilonen, J., Veijola, R., Knip, M., et al. (2013) · JAMA · doi:10.1001/jama.2013.6285 · Cited by 1,312 · see citing works
Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss
Thorel, F., Népote, V., Avril, I., Kohno, K., Desgraz, R., Chera, S., & Herrera, P. L. (2010) · Nature · doi:10.1038/nature08894 · Cited by 1,136 · see citing works
The role of inflammation in insulitis and β-cell loss in type 1 diabetes
Eizirik, D. L., Colli, M. L., & Ortis, F. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.21 · Cited by 1,011 · see citing works
Self-citationNejentsev, S., Walker, N., Riches, D., Egholm, M., & Todd, J. A. (2009) · Science · doi:10.1126/science.1167728 · Cited by 958 · see citing works
A choice of death - the signal-transduction of immune-mediated beta-cell apoptosis
Eizirik, D. L., & Mandrup-Poulsen, T. R. (2001) · Diabetologia · doi:10.1007/s001250100021 · Cited by 880 · see citing works
Self-citationShared and Distinct Genetic Variants in Type 1 Diabetes and Celiac Disease
Smyth, D. J., Plagnol, V., Walker, N. M., Cooper, J. D., Downes, K., Yang, J. H. M., Howson, J. M. M., Stevens, H. E., McManus, R., Wijmenga, C., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0807917 · Cited by 738 · see citing works
Önengüt-Gümüşcü, S., Chen, W., Burren, O. S., Cooper, N. J., Quinlan, A. R., Mychaleckyj, J. C., Farber, E., Bonnie, J. K., Szpak, M., Schofield, E. C., et al. (2015) · Nature Genetics · doi:10.1038/ng.3245 · Cited by 675 · see citing works
Coppieters, K. T., Dotta, F., Amirian, N., Campbell, P. D., Kay, T. W. H., Atkinson, M. A., Roep, B. O., & von Herrath, M. G. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20111187 · Cited by 672 · see citing works
Diabetes induced by Coxsackie virus: Initiation by bystander damage and not molecular mimicry
Horwitz, M. S., Bradley, L. M., Harbertson, J., Krahl, T., Lee, J., & Sarvennick, N. (1998) · Nature Medicine · doi:10.1038/nm0798-781 · Cited by 670 · see citing works
Dotta, F., Censini, S., van Halteren, A. G. S., Marselli, L., Masini, M., Dionisi, S., Mosca, F., Boggi, U., Muda, A. O., Prato, S. D., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700442104 · Cited by 569 · see citing works
MDA5/RIG-I and virus recognition
Takeuchi, O., & Akira, S. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.01.002 · Cited by 567 · see citing works
Todd, J. A. (2010) · Immunity · doi:10.1016/j.immuni.2010.04.001 · Cited by 560 · see citing works
Yan, N., & Chen, Z. J. (2012) · Nature Immunology · doi:10.1038/ni.2229 · Cited by 535 · see citing works
Concannon, P., Rich, S. S., & Nepom, G. T. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0808284 · Cited by 510 · see citing works
Yeung, W. G., Rawlinson, W. D., & Craig, M. E. (2011) · BMJ · doi:10.1136/bmj.d35 · Cited by 510 · see citing works
Meier, J. J., Bhushan, A., Butler, A. E., Rizza, R. A., & Butler, P. C. (2005) · Diabetologia · doi:10.1007/s00125-005-1949-2 · Cited by 493 · see citing works
Fattovich, G., Giustina, G., Favarato, S., & Ruol, A. (1996) · Journal of Hepatology · doi:10.1016/s0168-8278(96)80184-x · Cited by 483 · see citing works
Immune cell crosstalk in type 1 diabetes
Lehuen, A., Diana, J., Zaccone, P., & Cooke, A. (2010) · Nature reviews. Immunology · doi:10.1038/nri2787 · Cited by 478 · see citing works
Eizirik, D. L., Sammeth, M., Bouckenooghe, T., Bottu, G., Sisino, G., Igoillo-Esteve, M., Ortis, F., Santin, I., Colli, M. L., Barthson, J., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002552 · Cited by 465 · see citing works
Self-citationAtkinson, M. A., Bowman, M. A., Campbell, L., Darrow, B. L., Kaufman, D. L., & Maclaren, N. K. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117567 · Cited by 448 · see citing works
the TEDDY Study Group, Krischer, J. P., Lynch, K. F., Schatz, D. A., Ilonen, J., Lernmark, Å., Hagopian, W. A., Rewers, M. J., She, J.-X., Simell, O. G., et al. (2015) · Diabetologia · doi:10.1007/s00125-015-3514-y · Cited by 444 · see citing works
Diana, J., Simoni, Y., Furio, L., Beaudoin, L., Agerberth, B., Barrat, F. J., & Lehuen, A. (2012) · Nature Medicine · doi:10.1038/nm.3042 · Cited by 428 · see citing works
Viral Antibodies in Diabetes Mellitus
Gamble, D. R., Kinsley, M., Fitzgerald, M. G., Bolton, R., & Taylor, K. W. (1969) · BMJ · doi:10.1136/bmj.3.5671.627 · Cited by 412 · see citing works
Richardson, S. J., Willcox, A., Bone, A. J., Foulis, A. K., & Morgan, N. G. (2009) · Diabetologia · doi:10.1007/s00125-009-1276-0 · Cited by 384 · see citing works
Campbell, I. L., Kay, T. W. H., Oxbrow, L., & Harrison, L. C. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115055 · Cited by 376 · see citing works
Insulitis and β-Cell Mass in the Natural History of Type 1 Diabetes
Campbell‐Thompson, M., Fu, A. D., Kaddis, J. S., Wasserfall, C. H., Schatz, D., Pugliese, A., & Atkinson, M. A. (2015) · Diabetes · doi:10.2337/db15-0779 · Cited by 359 · see citing works
Zhernakova, A., Stahl, E. A., Trynka, G., Raychaudhuri, S., Festen, E. A. M., Franke, L., Westra, H.-J., Fehrmann, R. S. N., Kurreeman, F. A. S., Thomson, B. P., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002004 · Cited by 355 · see citing works
Concordance for islet autoimmunity among monozygotic twins
Redondo, M. J., Jeffrey, J., Fain, P. R., Eisenbarth, G. S., & Orban, T. (2008) · New England Journal of Medicine · doi:10.1056/nejmc0805398 · Cited by 353 · see citing works
Seasonal Incidence of Diabetes Mellitus
Gamble, D. R., & Taylor, K. W. (1969) · BMJ · doi:10.1136/bmj.3.5671.631 · Cited by 348 · see citing works
The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes
Wallace, C., Smyth, D. J., Maisuria-Armer, M., Walker, N. M., Todd, J. A., & Clayton, D. G. (2009) · Nature Genetics · doi:10.1038/ng.493 · Cited by 325 · see citing works
Krogvold, L., Edwin, B., Buanes, T., Frisk, G., Skog, O., Anagandula, M., Korsgren, O., Undlien, D., Eike, M. C., Richardson, S. J., et al. (2015) · Diabetes · doi:10.2337/db14-1370 · Cited by 314 · see citing works
Ferreira, R. C., Guo, H., Coulson, R., Smyth, D. J., Pękalski, M. Ł., Burren, O. S., Cutler, A. J., Doecke, J. D., Flint, S. M., McKinney, E. F., et al. (2014) · Diabetes · doi:10.2337/db13-1777 · Cited by 313 · see citing works
Genetics of Type 1 Diabetes: What's Next?
Pociot, F., Akolkar, B., CONCANNON, P. J., Erlich, H. A., Julier, C., Morahan, G., Nierras, C. R., Todd, J. A., Rich, S. S., & Nerup, J. (2010) · Diabetes · doi:10.2337/db10-0076 · Cited by 301 · see citing works
Cellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens
Randow, F., MacMicking, J. D., & James, L. C. (2013) · Science · doi:10.1126/science.1233028 · Cited by 294 · see citing works
Ylipaasto, P., Klingel, K., Lindberg, A., Otonkoski, T., Kandolf, R., Hovi, T., & Roivainen, M. (2004) · Diabetologia · doi:10.1007/s00125-003-1297-z · Cited by 294 · see citing works
A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk
Cardiogenics Consortium, Heinig, M., Petretto, E., Wallace, C., Bottolo, L., Rotival, M., Lu, H., Li, Y., Sarwar, R., Langley, S. R., et al. (2010) · Nature · doi:10.1038/nature09386 · Cited by 283 · see citing works
Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host
Hober, D., & Sauter, P. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.27 · Cited by 271 · see citing works
Cnop, M., Abdulkarim, B., Bottu, G., Cunha, D. A., Igoillo‐Esteve, M., Masini, M., Turatsinze, J., Griebel, T., Villate, O., Santín, I., et al. (2013) · Diabetes · doi:10.2337/db13-1383 · Cited by 261 · see citing works
Self-citationSelective inhibitors of picornavirus replication
Palma, A. M. D., Vliegen, I., Clercq, E. D., & Neyts, J. H. (2008) · Medicinal Research Reviews · doi:10.1002/med.20125 · Cited by 258 · see citing works
Coxsackievirus B1 Is Associated With Induction of β-Cell Autoimmunity That Portends Type 1 Diabetes
Laitinen, O. H., Honkanen, H., Pakkanen, O., Oikarinen, S., Hankaniemi, M. M., Huhtala, H., Ruokoranta, T. M., Lecouturier, V., André, P., Harju, R., et al. (2013) · Diabetes · doi:10.2337/db13-0619 · Cited by 257 · see citing works
Rapid on/off cycling of cytokine production by virus-specific CD8+ T cells
Slifka, M. K., Rodriguez, F., & Whitton, J. L. (1999) · Nature · doi:10.1038/43454 · Cited by 255 · see citing works
Interferon Expression in the Pancreases of Patients With Type I Diabetes
Huang, X., Yuang, J., Goddard, A. D., et al. (1995) · Diabetes · doi:10.2337/diab.44.6.658 · Cited by 246 · see citing works
Cnop, M., Hughes, S. J., Igoillo‐Esteve, M., Hoppa, M. B., Sayyed, F., van de Laar, L., Gunter, J. H., de Koning, E. J. P., Walls, G. V., Gray, D. W. G., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1562-x · Cited by 240 · see citing works
Bonifacio, E. E., Lampasona, V., Genovese, S., Ferrari, M., & Bosi, E. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.11.5419 · Cited by 236 · see citing works
Foulis, A. K., & Stewart, J. A. (1984) · Diabetologia · doi:10.1007/bf00262221 · Cited by 233 · see citing works
Cho, H., Proll, S. C., Szretter, K. J., Katze, M. G., Gale, M., & Diamond, M. S. (2013) · Nature Medicine · doi:10.1038/nm.3108 · Cited by 228 · see citing works
von Herrath, M. G., & Oldstone, M. B. A. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.3.531 · Cited by 223 · see citing works
Target cell defense prevents the development of diabetes after viral infection
Flodström‐Tullberg, M., Maday, A., Balakrishna, D., Cleary, M. M., Yoshimura, A., & Sarvetnick, N. (2002) · Nature Immunology · doi:10.1038/ni771 · Cited by 220 · see citing works
Savinov, A., Wong, F., Stonebraker, A. C., & Chervonsky, A. (2003) · Journal of Experimental Medicine · doi:10.1084/jem.20021378 · Cited by 220 · see citing works
SERREZE, D. V., Ottendorfer, E. W., Ellis, T. M., Gauntt, C. J., & Atkinson, M. A. (2000) · Diabetes · doi:10.2337/diabetes.49.5.708 · Cited by 217 · see citing works
Honeyman, M. C., Stone, N. L., & Harrison, L. C. (1998) · Molecular Medicine · doi:10.1007/bf03401920 · Cited by 212 · see citing works
Hiemstra, H. S., Schloot, N. C., van Veelen, P. A., Willemen, S. J. M., Franken, K. L. M. C., van Rood, J. J., de Vries, R. R. P., Chaudhuri, A., Behan, P. O., Drijfhout, J. W., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.071050898 · Cited by 209 · see citing works
Patterns of β-Cell Autoantibody Appearance and Genetic Associations During the First Years of Life
Ilonen, J., Hammais, A., Laine, A., Lempainen, J., Vaarala, O., Veijola, R., Simell, O., & Knip, M. (2013) · Diabetes · doi:10.2337/db13-0300 · Cited by 206 · see citing works
Bcl-2 proteins in diabetes: mitochondrial pathways of β-cell death and dysfunction
Gurzov, E. N., & Eizirik, D. L. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.03.001 · Cited by 205 · see citing works
Self-citationBodansky, H. J., Staines, A. S., Stephenson, C. R., Haigh, D., & Cartwright, R. (1992) · BMJ · doi:10.1136/bmj.304.6833.1020 · Cited by 200 · see citing works
Chehadeh, W., Kerr-Conte, J. A., Pattou, F. N., Alm, G., Lefèbvre, J., Wattré, P., & Hober, D. (2000) · Journal of Virology · doi:10.1128/jvi.74.21.10153-10164.2000 · Cited by 191 · see citing works
Interferon-α initiates type 1 diabetes in nonobese diabetic mice
Li, Q., Xu, B., Michie, S. A., Rubins, K., Schreriber, R. D., & McDevitt, H. O. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806439105 · Cited by 182 · see citing works
Nogueira, T. C., de Paula, F. M. M., Villate, O., Colli, M. L., de Moura, R. F., Cunha, D. A., Marselli, L., Marchetti, P., Cnop, M., Julier, C., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003532 · Cited by 178 · see citing works
Self-citationEhl, S. R., Hombach, J., Aichele, P., Hengartner, H., & Zinkernagel, R. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.7.1241 · Cited by 175 · see citing works
Moore, F., Colli, M. L., Cnop, M., Igoillo‐Esteve, M., Cardozo, A. K., Cunha, D. A., Bugliani, M., Marchetti, P., & Eizirik, D. L. (2009) · Diabetes · doi:10.2337/db08-1510 · Cited by 167 · see citing works
Self-citationThe gut microbiota and Type 1 Diabetes
Gülden, E., Wong, F. S., & Li, W. (2015) · Clinical Immunology · doi:10.1016/j.clim.2015.05.013 · Cited by 165 · see citing works
Chapman, N. M., & Kim, K. (2008) · Springer eBooks · doi:10.1007/978-3-540-75546-3_13 · Cited by 162 · see citing works
Oikarinen, S., Tauriainen, S., Hober, D., Lucas, B., Vazeou, A., Sioofy‐Khojine, A., Bozas, E., Muir, P., Honkanen, H., Ilonen, J., et al. (2013) · Diabetes · doi:10.2337/db13-0620 · Cited by 150 · see citing works
Atkinson, M. A., von Herrath, M., Powers, A. C., & Clare-Salzler, M. J. (2015) · Diabetes Care · doi:10.2337/dc15-0144 · Cited by 145 · see citing works
An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R signaling in CD4+ T cells
Long, S., Cerosaletti, K. M., Wan, J. Y., Ho, J.-C., Tatum, M., Wei, S., Shilling, H. G., & Buckner, J. H. (2010) · Genes and Immunity · doi:10.1038/gene.2010.54 · Cited by 143 · see citing works
Candidate genes for type 1 diabetes modulate pancreatic islet inflammation and β ‐cell apoptosis
Santín, I., & Eizirik, D. L. (2013) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12162 · Cited by 140 · see citing works
Self-citationSantín, I., Moore, F., Colli, M. L., Gurzov, E. N., Marselli, L., Marchetti, P., & Eizirik, D. L. (2011) · Diabetes · doi:10.2337/db11-0758 · Cited by 138 · see citing works
Self-citationButler, A. E., Galasso, R., Meier, J. J., Basu, R., Rizza, R. A., & Butler, P. C. (2007) · Diabetologia · doi:10.1007/s00125-007-0794-x · Cited by 137 · see citing works
Drescher, K. M., Kono, K., Bopegamage, S., Carson, S. D., & Tracy, S. (2004) · Virology · doi:10.1016/j.virol.2004.06.049 · Cited by 137 · see citing works
Richardson, S. J., Leete, P., Bone, A. J., Foulis, A. K., & Morgan, N. G. (2012) · Diabetologia · doi:10.1007/s00125-012-2745-4 · Cited by 137 · see citing works
Immunoregulatory mechanisms triggered by viral infections protect from type 1 diabetes in mice
Filippi, C. M., Estes, E. A., Oldham, J. E., & von Herrath, M. G. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38503 · Cited by 131 · see citing works
The Hygiene Hypothesis: An Explanation for the Increased Frequency of Insulin-Dependent DiabetesPreprint
Bach, J., & Chatenoud, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a007799 · Cited by 129 · see citing works
Microbiology: Ditch the term pathogen
Casadevall, A., & Pirofski, L. (2014) · Nature · doi:10.1038/516165a · Cited by 125 · see citing works
Bergholdt, R., Brorsson, C., Palleja, A., Berchtold, L. A., Fløyel, T., Bang-Berthelsen, C. H., Frederiksen, K. S., Jensen, L. J., Størling, J., & Pociot, F. (2012) · Diabetes · doi:10.2337/db11-1263 · Cited by 125 · see citing works
Kondrashova, A., Seiskari, T., Ilonen, J., Knip, M., & Hyöty, H. (2012) · Apmis · doi:10.1111/apm.12023 · Cited by 124 · see citing works
Induction, exacerbation and inhibition of allergic and autoimmune diseases by infection
Kamradt, T., Göggel, R., & Erb, K. J. (2005) · Trends in Immunology · doi:10.1016/j.it.2005.03.009 · Cited by 123 · see citing works
Marroquí, L., dos Santos, R. S., Fløyel, T., Grieco, F. A., Santín, I., Beeck, A. O. D., Marselli, L., Marchetti, P., Pociot, F., & Eizirik, D. L. (2015) · Diabetes · doi:10.2337/db15-0362 · Cited by 121 · see citing works
Self-citationA viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes
Christen, U., Edelmann, K. H., McGavern, D. B., Wolfe, T., Coon, B., Teague, M. K., Miller, S. D., Oldstone, M. B. A., & von Herrath, M. G. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22557 · Cited by 121 · see citing works
Minimal Bystander Activation of CD8 T Cells during the Virus-induced Polyclonal T Cell Response
Zarozinski, C. C., & Welsh, R. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.9.1629 · Cited by 116 · see citing works
Cure of prediabetic mice by viral infections involves lymphocyte recruitment along an IP-10 gradient
Christen, U., Benke, D., Wolfe, T., Rodrigo, E., Rhode, A., Hughes, A. C., Oldstone, M. B. A., & von Herrath, M. G. (2004) · Journal of Clinical Investigation · doi:10.1172/jci17005 · Cited by 116 · see citing works
Pancreatic α Cells are Resistant to Metabolic Stress-induced Apoptosis in Type 2 Diabetes
Marroquí, L., Masini, M., Merino, B., Grieco, F. A., Millard, I., Dubois, C., Quesada, I., Marchetti, P., Cnop, M., & Eizirik, D. L. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.03.012 · Cited by 114 · see citing works
Self-citationMarroquí, L., Santín, I., dos Santos, R. S., Marselli, L., Marchetti, P., & Eizirik, D. L. (2014) · Diabetes · doi:10.2337/db13-1443 · Cited by 113 · see citing works
Self-citationRecent progress in understanding coxsackievirus replication, dissemination, and pathogenesis
Sin, J., Mangale, V., Thienphrapa, W., Gottlieb, R. A., & Feuer, R. (2015) · Virology · doi:10.1016/j.virol.2015.06.006 · Cited by 106 · see citing works
Fløyel, T., Brorsson, C., Nielsen, L. B., Miani, M., Bang-Berthelsen, C. H., Friedrichsen, M., Overgaard, A. J., Berchtold, L. A., Wiberg, A., Poulsen, P., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402571111 · Cited by 104 · see citing works
Self-citationColli, M. L., Moore, F., Gurzov, E. N., Ortis, F., & Eizirik, D. L. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp474 · Cited by 103 · see citing works
Self-citationFulminant type 1 diabetes—an important subtype in East Asia
Imagawa, A., & Hanafusa, T. (2011) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1236 · Cited by 101 · see citing works
Mechanisms of the hygiene hypothesis — molecular and otherwise
Vercelli, D. (2006) · Current Opinion in Immunology · doi:10.1016/j.coi.2006.09.002 · Cited by 101 · see citing works
Reduced Expression of IFIH1 Is Protective for Type 1 Diabetes
Downes, K., Pękalski, M. Ł., Angus, K. L., Hardy, M. P., Nutland, S. L., Smyth, D. J., Walker, N. M., Wallace, C., & Todd, J. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012646 · Cited by 100 · see citing works
Krogvold, L., Skog, O., Sundström, G., Edwin, B., Buanes, T. A., Hanssen, K. F., Ludvigsson, J., Grabherr, M. G., Korsgren, O., & Dahl‐Jørgensen, K. (2015) · Diabetes · doi:10.2337/db14-1911 · Cited by 96 · see citing works
Schloot, N. C., Willemen, S. J. M., Duinkerken, G., Drijfhout, J. W., de Vries, R. R. P., & Roep, B. O. (2001) · Human Immunology · doi:10.1016/s0198-8859(01)00223-3 · Cited by 87 · see citing works
Cooke, A. (2008) · Immunology · doi:10.1111/j.1365-2567.2008.03009.x · Cited by 87 · see citing works
Reduced Expression of the MDA5 Gene IFIH1 Prevents Autoimmune Diabetes
Lincez, P. J., Shanina, I., & Horwitz, M. S. (2015) · Diabetes · doi:10.2337/db14-1223 · Cited by 83 · see citing works
Sandberg, J. ‐., Eizirik, D. L., & Sandler, S. (1997) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1997.3771275.x · Cited by 81 · see citing works
Self-citationPancreatic Pathology in Type 1 Diabetes Mellitus
Richardson, S. J., Morgan, N. G., & Foulis, A. K. (2014) · Endocrine Pathology · doi:10.1007/s12022-014-9297-8 · Cited by 80 · see citing works
Santín, I., Moore, F., Grieco, F. A., Marchetti, P., Brancolini, C., & Eizirik, D. L. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.158 · Cited by 80 · see citing works
Self-citationStrandell, E., Eizirik, D. L., & Sandler, S. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114657 · Cited by 77 · see citing works
Self-citationRichter, M., Duménil, G., Uzé, G., Fellous, M., & Pellegrini, S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.38.24723 · Cited by 75 · see citing works
Coxsackievirus can persist in murine pancreas by deletion of 5′ terminal genomic sequences
Tracy, S., Smithee, S., Alhazmi, A., & Chapman, N. M. (2014) · Journal of Medical Virology · doi:10.1002/jmv.24039 · Cited by 74 · see citing works
Analysis of pancreas tissue in a child positive for islet cell antibodies
Oikarinen, M., Tauriainen, S., Honkanen, T., Vuori, K. V., Karhunen, P. J., Vasama-Nolvi, C., Oikarinen, S., Verbeke, C. S., Blair, G. E., Rantala, I. S., et al. (2008) · Diabetologia · doi:10.1007/s00125-008-1107-8 · Cited by 74 · see citing works
Schulte, B. M., Bakkers, J. M. J. E., Lanke, K. H. W., Melchers, W. J. G., Westerlaken, C., Allebes, W. A., Aanstoot, H., Bruining, G. J., Adema, G. J., van Kuppeveld, F. J. M., et al. (2010) · Viral Immunology · doi:10.1089/vim.2009.0072 · Cited by 74 · see citing works
Richter, W., Mertens, T., Schoel, B., Muir, P., Ritzkowsky, A., Scherbaum, W. A., & Boehm, B. O. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.2.721 · Cited by 73 · see citing works
Morphometric evidence for a striking B-cell reduction at the clinical onset of type 1 diabetes
Kl�ppel, G., Drenck, C. R., Oberholzer, M., & Heitz, P. U. (1984) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf00737292 · Cited by 72 · see citing works
Reynier, F., Pachot, A., Paye, M., Xu, Q., Turrel-Davin, F., Petit, F., Hot, A., Auffray, C., Bendelac, N., Nicolino, M. P., et al. (2010) · Genes and Immunity · doi:10.1038/gene.2009.112 · Cited by 72 · see citing works
Innate antiviral signalling in the central nervous system
Carty, M., Reinert, L. S., Paludan, S. R., & Bowie, A. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.10.012 · Cited by 72 · see citing works
Tao, J., Zou, Y., Feng, X.-L., Li, J., Wang, F., Pan, F.-M., & Ye, D. (2010) · Molecular Biology Reports · doi:10.1007/s11033-010-0601-5 · Cited by 71 · see citing works
Kay, T. W. H., Campbell, I. L., Oxbrow, L., et al. (1991) · Diabetologia · doi:10.1007/bf00408350 · Cited by 71 · see citing works
Marroquí, L., Lopes, M., dos Santos, R. S., Grieco, F. A., Roivainen, M., Richardson, S. J., Morgan, N. G., Beeck, A. O. D., & Eizirik, D. L. (2015) · eLife · doi:10.7554/elife.06990 · Cited by 70 · see citing works
Self-citationType 1 Diabetes and Interferon Therapy
Nakamura, K., Kawasaki, E., Imagawa, A., Awata, T., Ikegami, H., Uchigata, Y., Kobayashi, T., Shimada, A., Nakanishi, K., Makino, H., et al. (2011) · Diabetes Care · doi:10.2337/dc10-2274 · Cited by 68 · see citing works
Winkler, C., Lauber, C., Adler, K., Grallert, H., Illig, T., Ziegler, A.-G., & Bonifacio, E. (2011) · Diabetes · doi:10.2337/db10-1269 · Cited by 68 · see citing works
SERREZE, D. V., Wasserfall, C. H., Ottendorfer, E., et al. (2004) · Journal of Virology · doi:10.1128/jvi.79.2.1045-1052.2005 · Cited by 68 · see citing works
Molecular Signatures Differentiate Immune States in Type 1 Diabetic Families
Chen, Y.-G., Cabrera, S. M., Jia, S., Kaldunski, M., Kramer, J., Cheong, S., Geoffrey, R., Roethle, M. F., Woodliff, J., Greenbaum, C., et al. (2014) · Diabetes · doi:10.2337/db14-0214 · Cited by 65 · see citing works
Role of Viruses and Other Microbes in the Pathogenesis of Type 1 Diabetes
Kondrashova, A., & Hyöty, H. (2014) · International Reviews of Immunology · doi:10.3109/08830185.2014.889130 · Cited by 64 · see citing works
Enteroviruses as causative agents in type 1 diabetes: loose ends or lost cause?
Morgan, N. G., & Richardson, S. J. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.08.002 · Cited by 63 · see citing works
Lempainen, J., Laine, A., Hammais, A., Toppari, J., Simell, O., Veijola, R., Knip, M., & Ilonen, J. (2015) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.05.005 · Cited by 63 · see citing works
A polymorphism in PTPN2 gene is associated with an earlier onset of type 1 diabetes
Espino‐Paisán, L., de la Calle, H., Fernández‐Arquero, M., Figueredo, M. Á., de la Concha, E. G., Urcelay, E., & Santiago, J. L. (2011) · Immunogenetics · doi:10.1007/s00251-010-0500-x · Cited by 60 · see citing works
Early IFN type I response: Learning from microbial evasion strategies
Coccia, E. M., & Battistini, A. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.03.005 · Cited by 58 · see citing works
Potential viral pathogenic mechanism in human type 1 diabetes
Schneider, D., & von Herrath, M. G. (2014) · Diabetologia · doi:10.1007/s00125-014-3340-7 · Cited by 57 · see citing works
Viral Infection of Engrafted Human Islets Leads to Diabetes
Gallagher, G. R., Brehm, M. A., Finberg, R. W., BARTON, B. A., Shultz, L. D., Greiner, D. L., Bortell, R., & Wang, J. P. (2014) · Diabetes · doi:10.2337/db14-1020 · Cited by 55 · see citing works
Willcox, A., Richardson, S. J., Bone, A. J., Foulis, A. K., & Morgan, N. G. (2011) · Diabetologia · doi:10.1007/s00125-011-2192-7 · Cited by 52 · see citing works
Rook, G. A. W., & Brunet, L. R. (2005) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2005.02112.x · Cited by 51 · see citing works
Izumi, K., Mine, K., Inoue, Y., Teshima, M., Ogawa, S., Kai, Y., Kurafuji, T., Hirakawa, K., Miyakawa, D., Ikeda, H., et al. (2015) · Nature Communications · doi:10.1038/ncomms7748 · Cited by 50 · see citing works
Interferon therapy in hepatitis C leading to chronic type 1 diabetes
Zornitzki, T. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i1.233 · Cited by 48 · see citing works
Anagandula, M. K., Richardson, S. J., Oberste, M. S., Sioofy‐Khojine, A., Hyöty, H., Morgan, N. G., Korsgren, O., & Frisk, G. (2013) · Journal of Medical Virology · doi:10.1002/jmv.23835 · Cited by 47 · see citing works
Neil, J. A., & Coulson, B. S. (2015) · Diabetologia · doi:10.1007/s00125-015-3562-3 · Cited by 47 · see citing works
Larsson, P. G., Lakshmikanth, T., Laitinen, O. H., Utorova, R., Jacobson, S., Oikarinen, M., Domsgen, E., Koivunen, M. R. L., Chaux, P., Devard, N., et al. (2014) · Diabetologia · doi:10.1007/s00125-014-3436-0 · Cited by 46 · see citing works
TYK2 Promoter Variant and Diabetes Mellitus in the Japanese
Nagafuchi, S., Hibio, Y., Hirakawa, K., Tsutsu, N., Minami, M., Okada, A., Kai, K., Teshima, M., Moroishi, A., Murakami, Y., et al. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.05.004 · Cited by 42 · see citing works
Tanaka, S. A., Aida, K., Nishida, Y., et al. (2013) · Endocrine Journal · doi:10.1507/endocrj.ej13-0222 · Cited by 41 · see citing works
Prevention or acceleration of type 1 diabetes by viruses
Ghazarian, L., Diana, J., Simoni, Y., Beaudoin, L., & Lehuen, A. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1042-1 · Cited by 40 · see citing works
Quah, H. S., Miranda‐Hernandez, S., Khoo, A., et al. (2013) · Diabetes · doi:10.2337/db13-1210 · Cited by 36 · see citing works
Persistent infection of human pancreatic cells with Coxsackievirus B4 is cured by fluoxetine
Alidjinou, E. K., Sané, F., Bertin, A., Caloone, D., & Hober, D. (2015) · Antiviral Research · doi:10.1016/j.antiviral.2015.01.010 · Cited by 34 · see citing works
Enteroviruses, hygiene and type 1 diabetes: toward a preventive vaccine
Drescher, K. M., von Herrath, M., & Tracy, S. (2014) · Reviews in Medical Virology · doi:10.1002/rmv.1815 · Cited by 32 · see citing works
Bonifacio, E. E., Krumsiek, J., Winkler, C., Theis, F. J., & Ziegler, A. (2013) · Acta Diabetologica · doi:10.1007/s00592-013-0526-2 · Cited by 32 · see citing works
Moëll, A., Skog, O., Åhlin, E., et al. (2009) · Journal of Medical Virology · doi:10.1002/jmv.21476 · Cited by 29 · see citing works
Antiviral treatment of Coxsackie B virus infection in human pancreatic islets
Berg, A., Olsson, A., Korsgren, O., & Frisk, G. (2006) · Antiviral Research · doi:10.1016/j.antiviral.2006.12.001 · Cited by 20 · see citing works
WIN 54954 treatment of mice infected with a diabetogenic strain of group B coxsackievirus
See, D. M., & Tilles, J. G. (1993) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.37.8.1593 · Cited by 18 · see citing works
Developing a vaccine for Type 1 diabetes through targeting enteroviral infections
Hyöty, H., & Knip, M. (2014) · Expert Review of Vaccines · doi:10.1586/14760584.2014.933078 · Cited by 17 · see citing works
Sarmiento, L., Cubas‐Dueñas, I., & Cabrera‐Rode, E. (2013) · MEDICC Review · doi:10.1590/s1555-79602013000100007 · Cited by 17 · see citing works
Cnop, M., Hughes, S. J., Igoillo‐Esteve, M., Hoppa, M. B., Sayyed, F., van de Laar, L., Gunter, J. H., de Koning, E. J. P., Walls, G. V., Gray, D. W. G., et al. (2009) · Cited by 16 · see citing works
Chabot, S., Fakhfakh, A., Béland, K., Lamarre, A., Oldstone, M. B. A., Álvarez, F., & Djilali-Saiah, I. (2012) · Journal of Autoimmunity · doi:10.1016/j.jaut.2012.10.002 · Cited by 13 · see citing works
(2013) · MEDICC Review · doi:10.37757/mr2013v15.n1.7 · Cited by 10 · see citing works
Modification of encephalomyocarditis virus-induced diabetes in mice by antiviral agents
Powers, R. D., Dotson, W. M., & Hayden, F. G. (1983) · Antiviral Research · doi:10.1016/0166-3542(83)90022-0 · Cited by 2 · see citing works
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Molecular mechanisms of ROS production and oxidative stress in diabetes
Newsholme, P., Cruzat, V. F., Keane, K. N., Carlessi, R., & de Bittencourt, P. I. H. (2016) · Biochemical Journal · doi:10.1042/bcj20160503c · Cited by 878 · see citing works
COVID-19 and cellular senescence
Schmitt, C. A., Tchkonia, T., Niedernhofer, L. J., Robbins, P. D., Kirkland, J. L., & Lee, S. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00785-2 · Cited by 153 · see citing works
COVID-19 as a trigger for type 1 diabetes
Wang, Y., Guo, H., Wang, G., Zhai, J., & Du, B. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad165 · Cited by 50 · see citing works
- Authors
- Op de Beeck, A., & Eizirik, D. L.
- Affiliations
- Université Libre de Bruxelles (BE)
- Corresponding author
- Eizirik, Decio L.
- ORCID
- Eizirik, Decio L.
- Venue
- Nature Reviews Endocrinology
- Published
- 2016-03-29
- Volume
- 12
- Issue
- 5
- Pages
- 263-273
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- PMC
- PMC5348720
- OpenAlex
- W2324838759
- Cited by
- 291
- References
- 146
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 37 · 2023: 38 · 2022: 36 · 2021: 44 · 2020: 37 · 2019: 10 · 2018: 30 · 2017: 18 · 2016: 6
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (UC4DK104166)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Keywords
- type 1 diabetes, viral triggers, enterovirus, Coxsackie virus, pancreatic beta cells, beta-cell apoptosis, environmental risk factors, antiviral innate immunity, MDA5, PTPN2, TYK2, viral clearance, prophylaxis
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Humans, Virus Diseases, Insulin-Secreting Cells
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