Skip to main content
SpringerLink
Log in

Laboratory Diagnosis of Enterovirus Infection: Optimal Methods for Studies of Diabetes

  • Chapter
  • First Online:
Diabetes and Viruses

  • 1435 Accesses

Abstract

Laboratory diagnosis of enterovirus infections is more complex than that of many other virus infections. Careful design of study protocols and sample collection procedures is crucial for studies evaluating the role of enteroviruses in type 1 diabetes. Possible viral persistence creates an additional challenge, since the virus may be present in low quantities and in the form of double-stranded RNA. Both direct virus detection and serology have their own advantages and disadvantages, depending on the individual research questions, technologies, and sample types used in the studies. In many cases, their combined use would give the best view on the relationship between enteroviruses and type 1 diabetes. Standardization of enterovirus assays by international collaboration would help identify the optimal diagnostic approaches for type 1 diabetes studies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Chapman NM, Kim KS, Drescher KM, Oka K, Tracy S (2008) 5′ terminal deletions in the genome of a coxsackievirus B2 strain occurred naturally in human heart. Virology 2:480–491

    Article  Google Scholar 

  • Chehadeh W, Kerr-Conte J, Pattou F, Alm G, Lefebvre J, Wattre P, Hober D (2000) Persistent infection of human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesis in beta cells. J Virol 21:10153–10164

    Article  Google Scholar 

  • Elfving M, Svensson J, Oikarinen S, Jonsson B, Olofsson P, Sundkvist G, Lindberg B, Lernmark A, Hyoty H, Ivarsson SA (2008) Maternal enterovirus infection during pregnancy as a risk factor in offspring diagnosed with type 1 diabetes between 15 and 30 years of age. Exp Diabetes Res 2008:271958

    Article  PubMed  Google Scholar 

  • Foulis AK (1996) The pathology of the endocrine pancreas in type 1 (insulin-dependent) diabetes mellitus. Acta Pathol Microbiol Immunol Scand 3:161–167

    Google Scholar 

  • Foulis AK, McGill M, Farquharson MA, Hilton DA (1997) A search for evidence of viral infection in pancreases of newly diagnosed patients with IDDM. Diabetologia 1:53–61

    Article  Google Scholar 

  • Harkonen T, Puolakkainen M, Sarvas M, Airaksinen U, Hovi T, Roivainen M (2000) Picornavirus proteins share antigenic determinants with heat shock proteins 60/65. J Med Virol 3:383–391

    Article  Google Scholar 

  • Harkonen T, Lankinen H, Davydova B, Hovi T, Roivainen M (2002) Enterovirus infection can induce immune responses that cross-react with beta-cell autoantigen tyrosine phosphatase IA-2/IAR. J Med Virol 3:340–350

    Article  Google Scholar 

  • Hohenadl C, Klingel K, Mertsching J, Hofschneider PH, Kandolf R (1991) Strand-specific detection of enteroviral RNA in myocardial tissue by in situ hybridization. Mol Cell Probes 1:11–20

    Article  Google Scholar 

  • Hovi T, Roivainen M (1993) Peptide antisera targeted to a conserved sequence in poliovirus capsid VP1 cross-react widely with members of the genus Enterovirus. J Clin Microbiol 5:1083–1087

    Google Scholar 

  • Hyöty H, Hiltunen M, Knip M, Laakkonen M, Vähäsalo P, Karjalainen J, Koskela P, Roivainen M, Leinikki P, Hovi T, Ã…kerblom HK, DiMe-study group (1995) A prospective study of the role of Coxsackie B and other enteroviruses in the pathogenesis of IDDM. Diabetes 44:652–657

    Article  PubMed  Google Scholar 

  • Imagawa A, Hanafusa T, Tamura S, Moriwaki M, Itoh N, Yamamoto K, Iwahashi H, Yamagata K, Waguri M, Nanmo T, Uno S, Nakajima H, Namba M, Kawata S, Miyagawa JI, Matsuzawa Y (2001) Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity. Diabetes 6:1269–1273

    Article  Google Scholar 

  • Klingel K, Hohenadl C, Canu A, Albrecht M, Seemann M, Mall G, Kandolf R (1992) Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation. Proc Natl Acad Sci U S A 1:314–318

    Article  Google Scholar 

  • Klingel K, Sauter M, Bock CT, Szalay G, Schnorr JJ, Kandolf R (2004) Molecular pathology of inflammatory cardiomyopathy. Med Microbiol Immunol 2–3:101–107

    Article  Google Scholar 

  • Kroneman A, Vennema H, Deforche K, v d Avoort H, Peñaranda S, Oberste MS, Vinjé J, Koopmans M (2011) An automated genotyping tool for enteroviruses and noroviruses. J Clin Virol 51(2):121–125

    Article  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 10:3108–3113

    Article  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 8:2698–2704

    Article  Google Scholar 

  • Oberste MS, Maher K, Kilpatrick DR, Flemister MR, Brown BA, Pallansch MA (1999a) Typing of human enteroviruses by partial sequencing of VP1. J Clin Microbiol 5:1288–1293

    Google Scholar 

  • Oberste MS, Maher K, Kilpatrick DR, Pallansch MA (1999b) Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. J Virol 3:1941–1948

    Google Scholar 

  • Oikarinen S, Tauriainen S, Viskari H, Simell O, Knip M, Virtanen S, Hyoty H (2009) PCR inhibition in stool samples in relation to age of infants. J Clin Virol 3:211–214

    Article  Google Scholar 

  • Oikarinen M, Tauriainen S, Penttila P, Keim J, Rantala I, Honkanen T, Hyoty H (2010) Evaluation of immunohistochemistry and in situ hybridization methods for the detection of enteroviruses using infected cell culture samples. J Clin Virol 3:224–228

    Article  Google Scholar 

  • Oikarinen S, Martiskainen M, Tauriainen S, Huhtala H, Ilonen J, Veijola R, Simell O, Knip M, Hyoty H (2011) Enterovirus RNA in blood is linked to the development of type 1 diabetes. Diabetes 1:276–279

    Article  Google Scholar 

  • Racaniello VR (2001) Picornaviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fields virology. Lippincott Williams & Wilkins, Philadelphia, pp 685–722

    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 6:1143–1151

    Article  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 3:180–185

    Article  Google Scholar 

  • Richardson SJ, Willcox A, Bone AJ, Morgan NG, Foulis AK (2011) Immunopathology of the human pancreas in type-I diabetes. Semin Immunopathol 1:9–21

    Article  Google Scholar 

  • Saliba GS, Franklin SL, Jackson GG (1968) ECHO-11 as a respiratory virus: quantitation of infection in man. J Clin Invest 6:1303–1313

    Article  Google Scholar 

  • Samuelson A, Forsgren M, Johansson B, Wahren B, Sallberg M (1994) Molecular basis for serological cross-reactivity between enteroviruses. Clin Diagn Lab Immunol 3:336–341

    Google Scholar 

  • Samuelson A, Forsgren M, Sallberg M (1995) Characterization of the recognition site and diagnostic potential of an enterovirus group-reactive monoclonal antibody. Clin Diagn Lab Immunol 3:385–386

    Google Scholar 

  • Schulte BM, Bakkers J, Lanke KH, Melchers WJ, Westerlaken C, Allebes W, Aanstoot HJ, Bruining GJ, Adema GJ, Van Kuppeveld FJ, Galama JM (2010) Detection of enterovirus RNA in peripheral blood mononuclear cells of type 1 diabetic patients beyond the stage of acute infection. Viral Immunol 1:99–104

    Article  Google Scholar 

  • Stene LC, Oikarinen S, Hyoty 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 12:3174–3180

    Article  Google Scholar 

  • Tam PE, Messner RP (1999) Molecular mechanisms of coxsackievirus persistence in chronic inflammatory myopathy: viral RNA persists through formation of a double-stranded complex without associated genomic mutations or evolution. J Virol 12:10113–10121

    Google Scholar 

  • Tapia G, Cinek O, Rasmussen T, Witso E, Grinde B, Stene LC, Ronningen 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 1:151–155

    Article  Google Scholar 

  • Tauriainen S, Oikarinen S, Oikarinen M, Hyoty H (2010) Enteroviruses in the pathogenesis of type 1 diabetes. Semin Immunopathol 1:45–55

    Google Scholar 

  • Terletskaia-Ladwig E, Meier S, Hahn R, Leinmuller M, Schneider F, Enders M (2008) A convenient rapid culture assay for the detection of enteroviruses in clinical samples: comparison with conventional cell culture and RT-PCR. J Med Microbiol 8:1000–1006

    Article  Google Scholar 

  • Torfason EG, Galindo R, Keyserling HL (1988) Comparison of five ELISA assays for IgG antibody against coxsackievirus B1. J Med Virol 1:53–60

    Article  Google Scholar 

  • Trabelsi A, Grattard F, Nejmeddine M, Aouni M, Bourlet T, Pozzetto B (1995) Evaluation of an enterovirus group-specific anti-VP1 monoclonal antibody, 5-D8/1, in comparison with neutralization and PCR for rapid identification of enteroviruses in cell culture. J Clin Microbiol 9:2454–2457

    Google Scholar 

  • Yagi S, Schnurr D, Lin J (1992) Spectrum of monoclonal antibodies to coxsackievirus B-3 includes type- and group-specific antibodies. J Clin Microbiol 9:2498–2501

    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. Br Med J 342:d35

    Article  Google Scholar 

  • Ylipaasto P, Klingel K, Lindberg AM, Otonkoski T, Kandolf R, Hovi T, Roivainen M (2004) Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells. Diabetologia 2:225–239

    Article  Google Scholar 

  • Yousef GE, Brown IN, Mowbray JF (1987) Derivation and biochemical characterization of an enterovirus group-specific monoclonal antibody. Intervirology 3:163–170

    Google Scholar 

Download references

Acknowledgments

We wish to thank the Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative type 1 diabetes research project sponsored by the Juvenile Diabetes Research Foundation International (JDRF) for the pancreas samples. Organ Procurement Organi­zations (OPO) partnering with nPOD to provide research resources are listed at www.jdrfnpod.org/our-partners.php. We thank Professor Markku Mäki and Dosent Katri Kaukinen for small intestine biopsy samples. Also we are grateful to The Juvenile Diabetes Research Foundation International, EU commission (PEVET Research Program, Grant Agreement Number 261441), and The Academy of Finland for funding our research.

Author information

Authors and Affiliations

  1. School of Medicine, University of Tampere, Tampere, Finland

    Sami Oikarinen M.D. & Maarit Oikarinen

Authors
  1. Sami Oikarinen M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maarit Oikarinen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sami Oikarinen M.D. .

Editor information

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

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Oikarinen, S., Oikarinen, M. (2013). Laboratory Diagnosis of Enterovirus Infection: Optimal Methods for Studies of Diabetes. 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_13

Download citation

Publish with us

Policies and ethics

Search

Navigation