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Enteroviruses in Blood

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Abstract

At the time of clinical diagnosis, the majority of children with type 1 diabetes carry EVs of different species in their blood. Controls rarely carry EVs in blood. In the blood, these viruses are present at very low titers and are minimally able to replicate in cell culture. At the time of clinical diagnosis, the presence of asymptomatic enterovirus infections is common among family members. The enterovirus types involved remain to be defined, but enteroviruses belonging to the B species appear particularly prevalent. Geographic and temporal clusters of enterovirus infection and type 1 diabetes have been documented in Northern Italy. It will be important to determine the length of persistence of enteroviruses in the blood of diabetic children. The results do not provide direct evidence for a causal relationship between enterovirus infection and diabetes, but strongly suggest that the association is not fortuitous.

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References

  • Al-Hello H, Paananen A, Eskelinen M, Ylipaasto P, Hovi T, Salmela K, Lukashev AN, Bobegamage S, Roivainen M (2008) An enterovirus strain isolated from diabetic child belongs to a genetic subcluster of echovirus 11, but is also neutralised with monotypic antisera to coxsackievirus A9. J Gen Virol 89:1949–1959

    Article  PubMed  CAS  Google Scholar 

  • Baj A, Monaco S, Zanusso G, Dall’Ora E, Bertolasi A, Toniolo A (2007) Virology of the ­post-polio syndrome. Fut Virol 2:183–192

    Article  Google Scholar 

  • Bonifacio E, Genovese S, Braghi S, Bazzigaluppi E, Lampasona V, Bingley PJ, Rogge L, Pastore MR, Bognetti E, Bottazzo GF, Gale EAM, Bosi E (1995a) Islet autoantibody markers in IDDM: risk assessment strategies yielding high sensitivity. Diabetologia 38:816–822

    Article  PubMed  CAS  Google Scholar 

  • Bonifacio E, Lampasona V, Genovese S, Ferrari M, Bosi E (1995b) 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. J Immunol 155:5419–5426

    PubMed  CAS  Google Scholar 

  • Cabrera-Rode E, Sarmiento L, Tiberti C, Molina G, Barrios J, Hernández D, Díaz-Horta O, Di Mario U (2003) Type 1 diabetes islet associated antibodies in subjects infected by echovirus 16. Diabetologia 46:1348–1353

    Article  PubMed  CAS  Google Scholar 

  • Cabrera-Rode E, Sarmiento L, Molina G, Pérez C, Arranz C, Galvan JA, Prieto M, Barrios J, Palomera R, Fonseca M, Mas P, Díaz-Díaz O, Díaz-Horta O (2005) Islet cell related antibodies and type 1 diabetes associated with echovirus 30 epidemic: a case report. J Med Virol 76:373–377

    Article  PubMed  CAS  Google Scholar 

  • Cai K, Qi D, Hou X, Wang O, Chen J, Deng B, Qian L, Liu X, Le Y (2011) MCP-1 upregulates amylin expression in murine pancreatic β cells through ERK/JNK-AP1 and NF-κB related signaling pathways independent of CCR2. PLoS One 6:e19559

    Article  PubMed  CAS  Google Scholar 

  • Cavalcante P, Barberis M, Cannone M, Baggi F, Antozzi C, Maggi L, Cornelio F, Barbi M, Didò P, Berrih-Aknin S, Mantegazza R, Bernasconi P (2010) Detection of poliovirus-infected macrophages in thymus of patients with myasthenia gravis. Neurology 74:1118–1126

    Article  PubMed  CAS  Google Scholar 

  • Champsaur H, Dussaix E, Samolyk D, Fabre M, Bach C, Assan R (1980) Diabetes and Coxsackie virus B5 infection. Lancet 1:251

    Article  PubMed  CAS  Google Scholar 

  • Chapman NM, Kim KS (2008) Persistent coxsackievirus infection: enterovirus persistence in chronic myocarditis and dilated cardiomyopathy. Curr Top Microbiol Immunol 323:275–292

    Article  PubMed  CAS  Google Scholar 

  • Chen Z, Chumakov K, Dragunsky E, Kouiavskaia D, Makiya M, Neverov A, Rezapkin G, Sebrell A, Purcell R (2011) Chimpanzee-human monoclonal antibodies for treatment of chronic poliovirus excretors and emergency postexposure prophylaxis. J Virol 85:4354–4362

    Article  PubMed  CAS  Google Scholar 

  • Coleman JR, Papamichail D, Skiena S, Futcher B, Wimmer E, Mueller S (2008) Virus attenuation by genome-scale changes in codon pair bias. Science 320:1784–1787

    Article  PubMed  CAS  Google Scholar 

  • Conaldi PG, Biancone L, Bottelli A, De Martino A, Camussi G, Toniolo A (1997) Distinct pathogenic effects of group B coxsackieviruses on human glomerular and tubular kidney cells. J Virol 71:9180–9187

    PubMed  CAS  Google Scholar 

  • Destombes J, Couderc T, Thiesson D, Girard S, Wilt SG, Blondel B (1997) Persistent poliovirus infection in mouse motoneurons. J Virol 71:1621–1628

    PubMed  CAS  Google Scholar 

  • Díaz-Horta O, Bello M, Cabrera-Rode E, Suárez J, Más P, García I, Abalos I, Jofra R, Molina G, Díaz-Díaz O, Di Mario U (2001) Echovirus 4 and type 1 diabetes mellitus. Autoimmunity 34:275–281

    Article  PubMed  Google Scholar 

  • Dotta F, Censini S, van Halteren AG, Marselli L, Masini M, Dionisi S, Mosca F, Boggi U, Muda AO, Prato SD, Elliott JF, Covacci A, Rappuoli R, Roep BO, Marchetti P (2007) Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci USA 104:5115–5120

    Article  PubMed  CAS  Google Scholar 

  • Feuer R, Ruller CM, An N, Tabor-Godwin JM, Rhoades RE, Maciejewski S, Pagarigan RR, Cornell CT, Crocker SJ, Kiosses WB, Pham-Mitchell N, Campbell IL, Whitton JL (2009) Viral persistence and chronic immunopathology in the adult central nervous system following Coxsackievirus infection during the neonatal period. J Virol 83:9356–9369

    Article  PubMed  CAS  Google Scholar 

  • Foxman EF, Iwasaki A (2011) Genome-virome interactions: examining the role of common viral infections in complex disease. Nat Rev Microbiol 9:254–264

    Article  PubMed  CAS  Google Scholar 

  • Fujioka S, Kitaura Y, Deguchi H, Shimizu A, Isomura T, Suma H, Sabbah HN (2004) Evidence of viral infection in the myocardium of American and Japanese patients with idiopathic dilated cardiomyopathy. Am J Cardiol 94:602–605

    Article  PubMed  Google Scholar 

  • Gorbea C, Makar KA, Pauschinger M, Pratt G, Bersola JL, Varela J, David RM, Banks L, Huang CH, Li H, Schultheiss HP, Towbin JA, Vallejo JG, Bowles NE (2010) A role for Toll-like receptor 3 variants in host susceptibility to enteroviral myocarditis and dilated cardiomyopathy. J Biol Chem 285:23208–23223

    Article  PubMed  CAS  Google Scholar 

  • Harvala H, Sharp CP, Ngole EM, Delaporte E, Peeters M, Simmonds P (2011) Detection and genetic characterization of enteroviruses circulating among wild populations of chimpanzees in Cameroon: relationship with human and simian enteroviruses. J Virol 85:4480–4486

    Article  PubMed  CAS  Google Scholar 

  • Hober D, Sauter P (2010) Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host. Nat Rev Endocrinol 6:279–289

    Article  PubMed  Google Scholar 

  • Hu YF, Yang F, Du J, Dong J, Zhang T, Wu ZQ, Xue Y, Jin Q (2011) Complete genome analysis of coxsackievirus A2, A4, A5, and A10 strains isolated from hand-foot-and-mouth disease patients in China revealing frequent recombination of human enterovirus A. J Clin Microbiol 49:2426–2434

    Article  PubMed  CAS  Google Scholar 

  • Jenson AB, Rosenberg HS, Notkins AL (1980) Pancreatic islet-cell damage in children with fatal viral infections. Lancet 2:354–358

    PubMed  CAS  Google Scholar 

  • Kelly EJ, Hadac EM, Cullen BR, Russell SJ (2010) MicroRNA antagonism of the picornaviral life cycle: alternative mechanisms of interference. PLoS Pathog 6:e1000820

    Article  PubMed  Google Scholar 

  • Lampasona V, Petrone A, Tiberti C, Capizzi M, Spoletini M, di Pietro S, Songini M, Bonicchio S, Giorgino F, Bonifacio E, Bosi E, Buzzetti R (2010) Zinc transporter 8 antibodies complement GAD and IA-2 antibodies in the identification and characterization of adult-onset autoimmune diabetes. Diabetes Care 33:104–108

    Article  PubMed  CAS  Google Scholar 

  • McWilliam Leitch EC, Cabrerizo M, Cardosa J, Harvala H, Ivanova OE, Kroes AC, Lukashev A, Muir P, Odoom J, Roivainen M, Susi P, Trallero G, Evans DJ, Simmonds P (2010) Evolutionary dynamics and temporal/geographical correlates of recombination in the human enterovirus echovirus types 9, 11, and 30. J Virol 84:9292–9300

    Article  PubMed  CAS  Google Scholar 

  • Miao LY, Pierce C, Gray-Johnson J, DeLotell J, Shaw C, Chapman N, Yeh E, Schnurr D, Huang YT (2009) Monoclonal antibodies to VP1 recognize a broad range of enteroviruses. J Clin Microbiol 47:3108–3113

    Article  PubMed  CAS  Google Scholar 

  • Naserke HE, Dozio N, Ziegler AG, Bonifacio E (1998) Comparison of a novel micro-assay for insulin autoantibodies with the conventional radiobinding assay. Diabetologia 41:681–683

    Article  PubMed  CAS  Google Scholar 

  • Nix WA, Oberste MS, Pallansch MA (2006) Sensitive, seminested PCR amplification of VP1 sequences for direct identification of all enterovirus serotypes from original clinical specimens. J Clin Microbiol 44:2698–2704

    Article  PubMed  CAS  Google Scholar 

  • Norder H, De Palma AM, Selisko B, Costenaro L, Papageorgiou N, Arnan C, Coutard B, Lantez V, De Lamballerie X, Baronti C, Solà M, Tan J, Neyts J, Canard B, Coll M, Gorbalenya AE, Hilgenfeld R (2011) Picornavirus non-structural proteins as targets for new anti-virals with broad activity. Antiviral Res 89:204–218

    Article  PubMed  CAS  Google Scholar 

  • Notkins AL (1979) The causes of diabetes. Sci Am 241:62–73

    Article  PubMed  CAS  Google Scholar 

  • Otonkoski T, Roivainen M, Vaarala O, Dinesen B, Leipälä JA, Hovi T, Knip M (2000) Neonatal type I diabetes associated with maternal echovirus 6 infection: a case report. Diabetologia 43:1235–1238

    Article  PubMed  CAS  Google Scholar 

  • Paananen A, Ylipaasto P, Rieder E, Hovi T, Galama J, Roivainen M (2003) Molecular and biological analysis of echovirus 9 strain isolated from a diabetic child. J Med Virol 69:529–537

    Article  PubMed  CAS  Google Scholar 

  • Pallansch MA, Oberste MS (2010) High degree of genetic diversity of non-polio enteroviruses identified in Georgia by environmental and clinical surveillance, 2002-2005. J Med Microbiol 59:1340–1347

    Article  PubMed  Google Scholar 

  • Rahnefeld A, Ebstein F, Albrecht N, Opitz E, Kuckelkorn U, Stangl K, Rehm A, Kloetzel PM, Voigt A (2011) Antigen presentation capacity of dendritic cells is impaired in ongoing enterovirus-myocarditis. Eur J Immunol 41:2774–2781

    Article  PubMed  CAS  Google Scholar 

  • Rhoades RE, Tabor-Godwin JM, Tsueng G, Feuer R (2011) Enterovirus infections of the central nervous system. Virology 411:288–305

    Article  PubMed  CAS  Google Scholar 

  • Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG (2009) The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia 52:1143–1151

    Article  PubMed  CAS  Google Scholar 

  • Richardson SJ, Willcox A, Hilton DA, Tauriainen S, Hyoty H, Bone AJ, Foulis AK, Morgan NG (2010) Use of antisera directed against dsRNA to detect viral infections in formalin-fixed paraffin-embedded tissue. J Clin Virol 49:180–185

    Article  PubMed  CAS  Google Scholar 

  • Richardson SJ, Willcox A, Bone AJ, Morgan NG, Foulis AK (2011) Immunopathology of the human pancreas in type-I diabetes. Semin Immunopathol 33:9–21

    Article  PubMed  CAS  Google Scholar 

  • Roivainen M, Klingel K (2010) Virus infections and type 1 diabetes risk. Curr Diab Rep 10:350–356

    Article  PubMed  CAS  Google Scholar 

  • Shibasaki S, Imagawa A, Tauriainen S, Iino M, Oikarinen M, Abiru H, Tamaki K, Seino H, Nishi K, Takase I, Okada Y, Uno S, Murase-Mishiba Y, Terasaki J, Makino H, Shimomura I, Hyöty H, Hanafusa T (2010) Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes. Endocr J 57:211–219

    Article  PubMed  CAS  Google Scholar 

  • Sosenko JM, Palmer JP, Rafkin-Mervis L, Krischer JP, Cuthbertson D, Matheson D, Skyler JS (2008) Glucose and C-peptide changes in the perionset period of type 1 diabetes in the Diabetes Prevention Trial-Type 1. Diabetes Care 31:2188–2192

    Article  PubMed  CAS  Google Scholar 

  • Stene LC, Oikarinen S, Hyöty H, Barriga KJ, Norris JM, Klingensmith G, Hutton JC, Erlich HA, Eisenbarth GS, Rewers M (2010) Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes 59:3174–3180

    Article  PubMed  CAS  Google Scholar 

  • Tapia G, Cinek O, Rasmussen T, Witsø E, Grinde B, Stene LC, Rønningen KS (2011) Human enterovirus RNA in monthly fecal samples and islet autoimmunity in Norwegian children with high genetic risk for type 1 diabetes: the MIDIA study. Diabetes Care 34:151–155

    Article  PubMed  Google Scholar 

  • Tauriainen S, Oikarinen S, Oikarinen M, Hyöty H (2011) Enteroviruses in the pathogenesis of type 1 diabetes. Semin Immunopathol 33:45–55

    Article  PubMed  CAS  Google Scholar 

  • Toniolo A, Federico G, Manocchio I, Onodera T (1988) Aetiology and pathogenesis of type-i diabetes: viruses. In: Besser GM, Bodanski JM, Cudworth AG (eds) Clinical diabetes: an illustrated text. Gower Medical Publ, London, pp 10.1–20

    Google Scholar 

  • Toniolo A, Maccari G, Federico G, Salvatoni A, Bianchi G, Baj A (2010) Are enterovirus infections linked to the early stages of type 1 diabetes? In: American Society for Microbiology 110th General Meeting, San Diego, CA, ST-902

    Google Scholar 

  • Tracy S, Drescher KM, Jackson JD, Kim K, Kono K (2010) Enteroviruses, type 1 diabetes and hygiene: a complex relationship. Rev Med Virol 20:106–116

    Article  PubMed  CAS  Google Scholar 

  • Vreugdenhil GR, Schloot NC, Hoorens A, Rongen C, Pipeleers DG, Melchers WJ, Roep BO, Galama JM (2000) Acute onset of type I diabetes mellitus after severe echovirus 9 infection: putative pathogenic pathways. Clin Infect Dis 31:1025–1031

    Article  PubMed  CAS  Google Scholar 

  • Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2011) 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 54:2417–2420

    Article  PubMed  CAS  Google Scholar 

  • Williams CH, Oikarinen S, Tauriainen S, Salminen K, Hyoty H, Stanway G (2006) Molecular analysis of an echovirus 3 strain isolated from an individual concurrently with appearance of islet cell and IA-2 autoantibodies. J Clin Microbiol 44:441–448

    Article  PubMed  CAS  Google Scholar 

  • Yeung WC, Rawlinson WD, Craig ME (2011) Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. BMJ 342:d35

    Article  PubMed  Google Scholar 

  • 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 300:1173–1179

    Article  PubMed  CAS  Google Scholar 

  • Yozwiak NL, Skewes-Cox P, Gordon A, Saborio S, Kuan G, Balmaseda A, Ganem D, Harris E, DeRisi JL (2010) Human enterovirus 109: a novel interspecies recombinant enterovirus isolated from a case of acute pediatric respiratory illness in Nicaragua. J Virol 84:9047–9058

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was financed by the CARIPLO Foundation, Milano, Italy (grant Ricerca Biomedica 2009-2577). The generous support of Gianni Valcavi, Attorney is gratefully acknowledged. Thanks to Abner Louis Notkins for inspiration and encouragement.

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Authors and Affiliations

  1. Laboratory of Microbiology, University of Insubria and Ospedale di Circolo, Varese, Italy

    Antonio Toniolo M.D., Giuseppe Maccari & Oscar Díaz-Horta

  2. Pediatric Endocrinology Unit, Department of Experimental Medicine, University of Insubria Medical School, Varese, Italy

    Alessandro Salvatoni

  3. Unit of Pediatric Endocrinology and Diabetes, Department of Reproductive Medicine and Child Development, University of Pisa Medical School, Pisa, Italy

    Giovanni Federico

  4. Laboratory of Microbiology, Department of Experimental Medicine, University of Insubria Medical School, Varese, Italy

    Andreina Baj

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  1. Antonio Toniolo M.D.
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  2. Alessandro Salvatoni
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  3. Giovanni Federico
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  4. Giuseppe Maccari
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  5. Oscar Díaz-Horta
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  6. Andreina Baj
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Correspondence to Antonio Toniolo M.D. .

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Editors and Affiliations

  1. Queen Mary's School of Medicine and Dent, Centre for Diabetes & Metabolic Medicine, Institute of Cell & Molecular Science, n/a, London, E1 2AT, United Kingdom

    Keith Taylor

  2. Tampere University Hospital, Department of Virology, University of Tampere, n/a, Tampere, 33520, Finland

    Heikki Hyöty

  3. University of Insubria & Ospedale di Cir, Varese, Italy

    Antonio Toniolo

  4. University College London Medical School, n/a, London, NW3 2PF, United Kingdom

    Arie J. Zuckerman

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Toniolo, A., Salvatoni, A., Federico, G., Maccari, G., Díaz-Horta, O., Baj, A. (2013). Enteroviruses in Blood. In: Taylor, K., Hyöty, H., Toniolo, A., Zuckerman, A. (eds) Diabetes and Viruses. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4051-2_15

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