{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:42:50Z","timestamp":1791423770633,"version":"4.3.3"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,3,20]]},"abstract":"<jats:p>\n                    Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic \u03b2 cells. Several studies have suggested an association between Coxsackie enterovirus seroconversion and onset of disease. However, a direct link between \u03b2 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\n                    <jats:italic>ex vivo<\/jats:italic>\n                    nucleotide sequencing, cell culture, and immunological studies demonstrated Coxsackie B4 enterovirus in specimens from three of the six diabetic patients. Infection was specific of \u03b2 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 \u03b2 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 \u03b2 cells in patients with type 1 diabetes and that infection is associated with inflammation and functional impairment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0700442104","type":"journal-article","created":{"date-parts":[[2007,3,14]],"date-time":"2007-03-14T20:40:18Z","timestamp":1173904818000},"page":"5115-5120","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":511,"title":["Coxsackie B4 virus infection of \u03b2 cells and natural killer cell insulitis in recent-onset type 1 diabetic patients"],"prefix":"10.1073","volume":"104","author":[{"given":"Francesco","family":"Dotta","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Endocrine and Metabolic Sciences, and Biochemistry, University of Siena, 53100 Siena, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Censini","sequence":"additional","affiliation":[{"name":"Cellular Microbiology and Bioinformatics Unit, Novartis Vaccines, Via Fiorentina 1, 53100 Siena, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid G. 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Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Mosca","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, 56126 Pisa, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"Boggi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, 56126 Pisa, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Onetti","family":"Muda","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Pathology, University of Rome \u201cLa Sapienza,\u201d 00185 Rome, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano Del","family":"Prato","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, 56126 Pisa, 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