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

Vehik, Kendra LU ; Lynch, Kristian F LU ; Wong, Matthew C ; Tian, Xiangjun ; Ross, Matthew C ; Gibbs, Richard A ; Ajami, Nadim J ; Petrosino, Joseph F ; Rewers, Marian and Toppari, Jorma , et al. (2019) In Nature Medicine 25(12). p.1865-1872
Abstract

Viruses are implicated in autoimmune destruction of pancreatic islet β cells, which results in insulin deficiency and type 1 diabetes (T1D)1-4. Certain enteroviruses can infect β cells in vitro5, have been detected in the pancreatic islets of patients with T1D6 and have shown an association with T1D in meta-analyses4. 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 viruses7 and the selection of variants with altered pathogenicity and ability to spread in populations. β cells strongly express cell-surface coxsackie and adenovirus receptor (CXADR) genes, which... (More)

Viruses are implicated in autoimmune destruction of pancreatic islet β cells, which results in insulin deficiency and type 1 diabetes (T1D)1-4. Certain enteroviruses can infect β cells in vitro5, have been detected in the pancreatic islets of patients with T1D6 and have shown an association with T1D in meta-analyses4. 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 viruses7 and the selection of variants with altered pathogenicity and ability to spread in populations. β cells strongly express cell-surface coxsackie and adenovirus receptor (CXADR) genes, which can facilitate enterovirus infection8. Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to β cells between serotypes and within the same serotype9,10. 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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published
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Nature Medicine
volume
25
issue
12
pages
8 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:31792456
  • scopus:85076031135
  • pmid:31792456
ISSN
1546-170X
DOI
10.1038/s41591-019-0667-0
language
English
LU publication?
yes
id
33b6fc7f-c50c-4790-8340-6d56762ebac5
date added to LUP
2019-12-13 00:52:36
date last changed
2024-12-27 03:22:26
@article{33b6fc7f-c50c-4790-8340-6d56762ebac5,
  abstract     = {{<p>Viruses are implicated in autoimmune destruction of pancreatic islet β cells, which results in insulin deficiency and type 1 diabetes (T1D)1-4. Certain enteroviruses can infect β cells in vitro5, have been detected in the pancreatic islets of patients with T1D6 and have shown an association with T1D in meta-analyses4. 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 viruses7 and the selection of variants with altered pathogenicity and ability to spread in populations. β cells strongly express cell-surface coxsackie and adenovirus receptor (CXADR) genes, which can facilitate enterovirus infection8. Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to β cells between serotypes and within the same serotype9,10. 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.</p>}},
  author       = {{Vehik, Kendra and Lynch, Kristian F and Wong, Matthew C and Tian, Xiangjun and Ross, Matthew C and Gibbs, Richard A and Ajami, Nadim J and Petrosino, Joseph F and Rewers, Marian and Toppari, Jorma and Ziegler, Anette G and She, Jin-Xiong and Lernmark, Ake and Akolkar, Beena and Hagopian, William A and Schatz, Desmond A and Krischer, Jeffrey P and Hyöty, Heikki and Lloyd, Richard E}},
  issn         = {{1546-170X}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{1865--1872}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Prospective virome analyses in young children at increased genetic risk for type 1 diabetes}},
  url          = {{http://dx.doi.org/10.1038/s41591-019-0667-0}},
  doi          = {{10.1038/s41591-019-0667-0}},
  volume       = {{25}},
  year         = {{2019}},
}