Coxsackie B4 virus infection of β cells and natural killer cell insulitis in recent-onset type 1 diabetic patients

Francesco Dotta, Stefano Censini, Astrid G.S. Van Halteren, Lorella Marselli, Matilde Masini, Sabrina Dionisi, Franco Mosca, Ugo Boggi, Andrea Onetti Muda, Stefano Del Prato, John F. Elliott, Antonello Covacci, Rino Rappuoli, Bart O. Roep, Piero Marchetti

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

467 Citaten (Scopus)

Samenvatting

Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic β cells. Several studies have suggested an association between Coxsackie enterovirus seroconversion and onset of disease. However, a direct link between β cell viral infection and islet inflammation has not been established. We analyzed pancreatic tissue from six type 1 diabetic and 26 control organ donors. Immunohistochemical, electron microscopy, whole-genome ex vivo nucleotide sequencing, cell culture, and immunological studies demonstrated Coxsackie B4 enterovirus in specimens from three of the six diabetic patients. Infection was specific of β cells, which showed nondestructive islet inflammation mediated mainly by natural killer cells. Islets from enterovirus-positive samples displayed reduced insulin secretion in response to glucose and other secretagogues. In addition, virus extracted from positive islets was able to infect β cells from human islets of nondiabetic donors, causing viral inclusions and signs of pyknosis. None of the control organ donors showed signs of viral infection. These studies provide direct evidence that enterovirus can infect β cells in patients with type 1 diabetes and that infection is associated with inflammation and functional impairment.

Originele taal-2Engels
Pagina's (van-tot)5115-5120
Aantal pagina's6
TijdschriftProceedings of the National Academy of Sciences of the United States of America
Volume104
Nummer van het tijdschrift12
DOI's
StatusGepubliceerd - 20 mrt. 2007
Extern gepubliceerdJa

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