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Vehik, K.* ; Lynch, K.F.* ; Wong, M.C.* ; Tian, X.* ; Ross, M.C.* ; Gibbs, R.A.* ; Ajami, N.J.* ; Petrosino, J.F.* ; Rewers, M.* ; Toppari, J.* ; Ziegler, A.-G. ; She, J.X.* ; Lernmark, A.* ; Akolkar, B.* ; Hagopian, W.A.* ; Schatz, D.A.* ; Krischer, J.P.* ; Hyöty, H.* ; Lloyd, R.E.*

Prospective virome analyses in young children at increased genetic risk for type 1 diabetes.

Nat. Med. 25, 1865-1872 (2019)
Postprint DOI PMC
Open Access Green
Viruses are implicated in autoimmune destruction of pancreatic islet beta cells, which results in insulin deficiency and type 1 diabetes (T1D)(1-4). Certain enteroviruses can infect beta cells in vitro(5), have been detected in the pancreatic islets of patients with T1D(6) and have shown an association with T1D in meta-analyses(4). However, establishing consistency in findings across studies has proven difficult. Obstacles to convincingly linking RNA viruses to islet autoimmunity may be attributed to rapid viral mutation rates, the cyclical periodicity of viruses(7) and the selection of variants with altered pathogenicity and ability to spread in populations. beta cells strongly express cell-surface coxsackie and adenovirus receptor (CXADR) genes, which can facilitate enterovirus infection(8). Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to beta cells between serotypes and within the same serotype(9,10). In this large-scale study of known eukaryotic DNA and RNA viruses in stools from children, we evaluated fecally shed viruses in relation to islet autoimmunity and T1D. This study showed that prolonged enterovirus B rather than independent, short-duration enterovirus B infections may be involved in the development of islet autoimmunity, but not T1D, in some young children. Furthermore, we found that fewer early-life human mastadenovirus C infections, as well as CXADR rs6517774, independently correlated with islet autoimmunity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Beta-cell Autoimmunity; Islet Autoimmunity; Coxsackievirus B1; Enterovirus Rna; Environmental Determinants; Gut Microbiome; Induction; Infection; Receptor; Surveillance
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Zeitschrift Nature medicine
Quellenangaben Band: 25, Heft: 12, Seiten: 1865-1872 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research Type 1 (IDF)