1887

Abstract

(LV), a of the family, first isolated from a bank vole at the Ljungan river in Sweden, has been implicated in the risk for autoimmune type 1 diabetes. An assay for neutralizing Ljungan virus antibodies (NLVA) was developed using the original 87–012 LV isolate. The goal was to determine NLVA titres in incident 0–18 years old newly diagnosed type 1 diabetes patients (=67) and school children controls (=292) from Jämtland county in Sweden. NLVA were found in 41 of 67 (61 %) patients compared to 127 of 292 (44 %) controls (=0.009). In the type 1 diabetes patients, NLVA titres were associated with autoantibodies to glutamic acid decarboxylase (GADA) (=0.023), but not to autoantibodies against insulin (IAA) or islet antigen-2 (IA-2A). The NLVA assay should prove useful for further investigations to determine levels of LV antibodies in patients and future studies to determine a possible role of LV in autoimmune type 1 diabetes.

Funding
This study was supported by the:
  • Stiftelsen Axel Tielmans Minnesfond
    • Principle Award Recipient: AnnikaLundstig
  • H.K.H. Kronprinsessan Lovisas Förening för Barnasjukvård (SE)
    • Principle Award Recipient: AnnikaLundstig
  • Stiftelsen Familjen Ernfors Fond
    • Principle Award Recipient: AnnikaLundstig
  • Sven Mattssons Stiftelse
    • Principle Award Recipient: AnnikaLundstig
  • Lunds Revisorer
    • Principle Award Recipient: AnnikaLundstig
  • Lisa och Johan Grönbergs Stiftelse
    • Principle Award Recipient: AnnikaLundstig
  • Sydvästra Skånes Diabetesförening
    • Principle Award Recipient: AnnikaLundstig
  • Stiftelsen Olle Engkvist Byggmästare
    • Principle Award Recipient: AnnikaLundstig
  • The Swedish Child Diabetes Foundation
    • Principle Award Recipient: AnnikaLundstig
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/content/journal/jgv/10.1099/jgv.0.001602
2021-05-21
2022-01-24
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References

  1. Niklasson B, Kinnunen L, Hornfeldt B, Horling J, Benemar C. A new picornavirus isolated from bank voles (Clethrionomys glareolus. Virology 1999; 255:86–93 [View Article][PubMed]
    [Google Scholar]
  2. Johansson S, Niklasson B, Maizel J, Gorbalenya AE, Lindberg AM. Molecular analysis of three Ljungan virus isolates reveals a new, close-to-root lineage of the Picornaviridae with a cluster of two unrelated 2A proteins. J Virol 2002; 76:8920–8930 [View Article][PubMed]
    [Google Scholar]
  3. Johansson ES, Niklasson B, Tesh RB, Shafren DR, Travassos da Rosa AP. Molecular characterization of M1146, an American isolate of Ljungan virus (LV) reveals the presence of a new LV genotype. J Gen Virol 2003; 84:837–844 [View Article][PubMed]
    [Google Scholar]
  4. Niklasson B, Hultman T, Kallies R, Niedrig M, Nilsson R. The BioBreeding rat diabetes model is infected with Ljungan virus. Diabetologia 2007; 50:1559–1560 [View Article][PubMed]
    [Google Scholar]
  5. Hauffe HC, Niklasson B, Olsson T, Bianchi A, Rizzoli A. Ljungan virus detected in bank voles (Myodes glareolus) and yellow-necked mice (Apodemus flavicollis) from Northern Italy. J Wildl Dis 2010; 46:262–266 [View Article][PubMed]
    [Google Scholar]
  6. Salisbury AM, Begon M, Dove W, Niklasson B, Stewart JP. Ljungan virus is endemic in rodents in the UK. Arch Virol 2014; 159:547–551 [View Article][PubMed]
    [Google Scholar]
  7. Mitake H, Fujii Y, Nagai M, Ito N, Okadera K. Isolation of a sp. nov. Ljungan virus from wild birds in Japan. J Gen Virol 2016; 97:1818–1822 [View Article][PubMed]
    [Google Scholar]
  8. Fevola C, Rossi C, Rosso F, Girardi M, Rosà R et al. Geographical distribution of LJUNGAN virus in small mammals in Europe. Vector Borne Zoonotic Dis 2020; 20:692–702 [View Article][PubMed]
    [Google Scholar]
  9. Niklasson B, Hornfeldt B, Lundman B. Could myocarditis, insulin-dependent diabetes mellitus, and Guillain-Barre syndrome be caused by one or more infectious agents carried by rodents?. Emerg Infect Dis 1998; 4:187–193 [View Article][PubMed]
    [Google Scholar]
  10. Warvsten A, Bjornfors M, Arvidsson M, Vaziri-Sani F, Jonsson I. Islet autoantibodies present in association with Ljungan virus infection in bank voles (Myodes glareolus) in northern Sweden. J Med Virol 2017; 89:24–31 [View Article][PubMed]
    [Google Scholar]
  11. Nilsson A-. L, Lagerquist E, Lynch KF, Lernmark A, Rolandsson O. Temporal variation of Ljungan virus antibody levels in relation to islet autoantibodies and possible correlation to childhood type 1 diabetes. Opn Pediatr Med J 2009; 3:61–66
    [Google Scholar]
  12. Nilsson AL, Vaziri-Sani F, Andersson C, Larsson K, Carlsson A. Relationship between Ljungan virus antibodies, HLA-DQ8, and insulin autoantibodies in newly diagnosed type 1 diabetes children. Viral Immunol 2013; 26:207–215 [View Article][PubMed]
    [Google Scholar]
  13. Nilsson AL, Vaziri-Sani F, Broberg P, Elfaitouri A, Pipkorn R. Serological evaluation of possible exposure to Ljungan virus and related parechovirus in autoimmune (type 1) diabetes in children. J Med Virol 2015; 87:1130–1140 [View Article][PubMed]
    [Google Scholar]
  14. Niklasson B, Heller KE, Schonecker B, Bildsoe M, Daniels T. Development of type 1 diabetes in wild bank voles associated with islet autoantibodies and the novel ljungan virus. Int J Exp Diabesity Res 2003; 4:35–44 [View Article]
    [Google Scholar]
  15. Niklasson B. Current views on Ljungan virus and its relationship to human diabetes. J Med Virol 2011; 83:1673 [View Article][PubMed]
    [Google Scholar]
  16. Jaaskelainen AJ, Kolehmainen P, Voutilainen L, Hauffe HC, Kallio-Kokko H. Evidence of Ljungan virus specific antibodies in humans and rodents. J Med Virol 2013; 85:2001–2008 [View Article][PubMed]
    [Google Scholar]
  17. Jaaskelainen AJ, Voutilainen L, Lehmusto R, Henttonen H, Lappalainen M. Serological survey in the Finnish human population implies human-to-human transmission of Ljungan virus or antigenically related viruses. Epidemiol Infect 2016; 144:1278–1285 [View Article][PubMed]
    [Google Scholar]
  18. Weldon WC, Oberste MS, Pallansch MA. Standardized methods for detection of poliovirus antibodies. Methods Mol Biol 2016; 1387:145–176 [View Article][PubMed]
    [Google Scholar]
  19. Harrison CJ, Weldon WC, Pahud BA, Jackson MA, Oberste MS. Neutralizing antibody against enterovirus D68 in children and adults before 2014 outbreak, Kansas City, Missouri, USA. Emerg Infect Dis 2019; 25:585–588 [View Article][PubMed]
    [Google Scholar]
  20. Delli AJ, Vaziri-Sani F, Lindblad B, Elding-Larsson H, Carlsson A. Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the Better Diabetes Diagnosis study. Diabetes 2012; 61:2556–2564 [View Article][PubMed]
    [Google Scholar]
  21. Vaziri-Sani F, Delli AJ, Elding-Larsson H, Lindblad B, Carlsson A. A novel triple mix radiobinding assay for the three ZnT8 (ZnT8-RWQ) autoantibody variants in children with newly diagnosed diabetes. J Immunol Methods 2011; 371:25–37 [View Article][PubMed]
    [Google Scholar]
  22. Abadie A. Bootstrap tests for distributional treatment effects in instrumental variable models. J Am Stat Assoc 2002; 97:284–292 [View Article]
    [Google Scholar]
  23. CK Y, Chen CC, Chen CL, Wang JR, Liu CC. Neutralizing antibody provided protection against enterovirus type 71 lethal challenge in neonatal mice. J Biomed Sci 2000; 7:523–528
    [Google Scholar]
  24. Westerhuis BM, Benschop KSM, Koen G, Claassen YB, Wagner K et al. Human memory B cells producing potent cross-neutralizing antibodies against human parechovirus: Implications for prevalence, treatment, and diagnosis. J Virol 2015; 89:7457–7464 [View Article][PubMed]
    [Google Scholar]
  25. Jääskeläinen AJ, Nurminen N, Kolehmainen P, Smura T, Tauriainen S et al. No association between Ljungan virus seropositivity and the beta-cell damaging process in the finnish type 1 diabetes prediction and prevention study cohort. Pediatr Infect Dis J 2019; 38:314–316 [View Article][PubMed]
    [Google Scholar]
  26. Tolf C, Gullberg M, Johansson ES, Tesh RB, Andersson B. Molecular characterization of a novel Ljungan virus (Parechovirus; Picornaviridae) reveals a fourth genotype and indicates ancestral recombination. J Gen Virol 2009; 90:843–853 [View Article][PubMed]
    [Google Scholar]
  27. Tolf C, Gullberg M, Ekstrom JO, Jonsson N, Michael Lindberg A. Identification of amino acid residues of Ljungan virus VP0 and VP1 associated with cytolytic replication in cultured cells. Arch Virol 2009; 154:1271–1284 [View Article][PubMed]
    [Google Scholar]
  28. Nilsson AL, Vaziri-Sani F, Broberg P, Elfaitouri A, Pipkorn R. Serological evaluation of possible exposure to Ljungan virus and related parechovirus in autoimmune (type 1) diabetes in children. J Med Virol 2015; 87:1130–1140 [View Article][PubMed]
    [Google Scholar]
  29. Hyoty H. Viruses in type 1 diabetes. Pediatr Diabetes 2016; 17:56–64 [View Article]
    [Google Scholar]
  30. Vehik K, Lynch KF, Wong MC, Tian X, Ross MC. Prospective virome analyses in young children at increased genetic risk for type 1 diabetes. Nat Med 2019; 25:1865–1872 [View Article][PubMed]
    [Google Scholar]
  31. Krischer JP, Lynch KF, Schatz DA, Ilonen J, Lernmark A. The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia 2015; 58:980–987 [View Article][PubMed]
    [Google Scholar]
  32. Krischer JP, Liu X, Å L, Hagopian WA, Rewers MJ. The influence of type 1 diabetes genetic susceptibility regions, age, sex, and family history on the progression from multiple autoantibodies to type 1 diabetes: A TEDDY study report. Diabetes 2017; 66:3122–3129 [View Article]
    [Google Scholar]
  33. Krischer JP, Liu X, Vehik K, Akolkar B, Hagopian WA et al. Predicting islet cell autoimmunity and type 1 diabetes: An 8-year TEDDY study progress report. Diabetes Care 2019; 42:1051–1060 [View Article][PubMed]
    [Google Scholar]
  34. Ilonen J, Hammais A, Laine AP, Lempainen J, Vaarala O. Patterns of beta-cell autoantibody appearance and genetic associations during the first years of life. Diabetes 2013; 62:3636–3640 [View Article][PubMed]
    [Google Scholar]
  35. Krischer JP, Liu X, Lernmark A, Hagopian WA, Rewers MJ. The influence of type 1 diabetes genetic susceptibility regions, age, sex, and family history to the progression from multiple autoantibodies to type 1 diabetes: a TEDDY study report. Diabetes 2017; 66:3122–3129 [View Article][PubMed]
    [Google Scholar]
  36. Krischer JP, Lynch KF, Lernmark Å, Hagopian WA, Rewers MJ et al. Genetic and environmental interactions modify the risk of diabetes-related autoimmunity by 6 years of age: The TEDDY study. Diabetes Care 2017; 40:1194–1202 [View Article][PubMed]
    [Google Scholar]
  37. Stene LC, Oikarinen S, Hyoty H, Barriga KJ, Norris JM. Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY. Diabetes 2010; 59:3174–3180 [View Article][PubMed]
    [Google Scholar]
  38. Sioofy-Khojine AB, Lehtonen J, Nurminen N, Laitinen OH, Oikarinen S. Coxsackievirus B1 infections are associated with the initiation of insulin-driven autoimmunity that progresses to type 1 diabetes. Diabetologia 2018; 61:1193–1202 [View Article][PubMed]
    [Google Scholar]
  39. Zhao G, Vatanen T, Droit L, Park A, Kostic AD. Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children. Proc Natl Acad Sci U S A 2017; 114:E6166–E6175 [View Article][PubMed]
    [Google Scholar]
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