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

TitleProspective virome analyses in young children at increased genetic risk for type 1 diabetes.
Publication TypeJournal Article
Year of Publication2019
AuthorsVehik, K, Lynch, KF, Wong, MC, Tian, X, Ross, MC, Gibbs, RA, Ajami, NJ, Petrosino, JF, Rewers, M, Toppari, J, Ziegler, AG, She, J-X, Lernmark, A, Akolkar, B, Hagopian, WA, Schatz, DA, Krischer, JP, Hyoty, H, Lloyd, RE
Corporate AuthorsTEDDY Study Group
JournalNat Med
Volume25
Issue12
Pagination1865-1872
Date Published2019 12
ISSN1546-170X
KeywordsAdolescent, Autoimmunity, Child, Child, Preschool, Diabetes Mellitus, Type 1, Enterovirus, Feces, Female, Humans, Infant, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Male, Pancreas, RNA, Viral
Abstract

Viruses are implicated in autoimmune destruction of pancreatic islet β cells, which results in insulin deficiency and type 1 diabetes (T1D). Certain enteroviruses can infect β cells in vitro, have been detected in the pancreatic islets of patients with T1D and have shown an association with T1D in meta-analyses. 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 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 infection. Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to β cells between serotypes and within the same serotype. 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.

DOI10.1038/s41591-019-0667-0
Alternate JournalNat Med
PubMed ID31792456
PubMed Central IDPMC6898786
Grant ListU01 DK063821 / DK / NIDDK NIH HHS / United States
UC4 DK063863 / DK / NIDDK NIH HHS / United States
UL1 TR002535 / TR / NCATS NIH HHS / United States
HHSN267200700014C / DK / NIDDK NIH HHS / United States
U01 DK063861 / DK / NIDDK NIH HHS / United States
U01 DK063790 / DK / NIDDK NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UL1 TR000064 / TR / NCATS NIH HHS / United States
HHSN267200700014C / LM / NLM NIH HHS / United States
U01 DK063836 / DK / NIDDK NIH HHS / United States
U01 DK063829 / DK / NIDDK NIH HHS / United States
U01 DK063865 / DK / NIDDK NIH HHS / United States
UC4 DK095300 / DK / NIDDK NIH HHS / United States
UC4 DK063861 / DK / NIDDK NIH HHS / United States
UC4 DK063829 / DK / NIDDK NIH HHS / United States
UC4 DK063821 / DK / NIDDK NIH HHS / United States
UC4 DK117483 / DK / NIDDK NIH HHS / United States
UC4 DK063836 / DK / NIDDK NIH HHS / United States
UC4 DK112243 / DK / NIDDK NIH HHS / United States
UC4 DK063865 / DK / NIDDK NIH HHS / United States
U01 DK063863 / DK / NIDDK NIH HHS / United States
UC4 DK106955 / DK / NIDDK NIH HHS / United States
UC4 DK100238 / DK / NIDDK NIH HHS / United States