Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells

• Published in: Diabetologia Vol. 47; no. 2; pp. 225 - 239
• Main Authors: YLIPAASTO, P, KLINGEL, K, LINDBERG, A. M, OTONKOSKI, T, KANDOLF, R, HOVI, T, ROIVAINEN, M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-02-2004; Springer Nature B.V
• Subjects: Adenoviruses; Adolescent; Adult; Antibodies, Monoclonal - pharmacology; Autopsies; Autopsy; Beta cells; Biological and medical sciences; Cell Survival - drug effects; Cells; Cells, Cultured; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Coxsackievirus echovirus; Coxsackievirus Infections - pathology; Diabetes; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - virology; Diabetes. Impaired glucose tolerance; Echovirus 9 - genetics; Echovirus 9 - growth & development; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enterovirus; Enterovirus - genetics; Enterovirus - growth & development; Enterovirus B, Human - genetics; Enterovirus B, Human - growth & development; Enterovirus Infections - pathology; Human pancreas; Humans; Immunoglobulins; In Situ Hybridization; Infant; Infant, Newborn; Infections; Inflammation - pathology; Inflammation - virology; Insulin - analysis; Insulin - immunology; Insulin - metabolism; Insulin Secretion; Integrin alphaVbeta3 - analysis; Integrin alphaVbeta3 - immunology; Integrin alphaVbeta3 - metabolism; Islets; Islets of Langerhans - drug effects; Islets of Langerhans - pathology; Islets of Langerhans - virology; Laboratories; Medical sciences; MEDICIN; MEDICINE; Membrane Proteins - analysis; Membrane Proteins - immunology; Membrane Proteins - metabolism; Microbiology; Microbiology, immunology, infectious diseases; Microscopy, Fluorescence; Middle Aged; Mikrobiologi; Mikrobiologi, immunologi, infektionssjukdomar; Pancreas; Pancreas - chemistry; Pancreas - pathology; Pancreas - virology; Parechovirus - genetics; Parechovirus - growth & development; Poliovirus; Poliovirus - genetics; Poliovirus - growth & development; Public health; Receptors; Receptors, Virus - analysis; Receptors, Virus - immunology; Receptors, Virus - metabolism; RNA, Viral - genetics; Viral infections; Virologi; Virology; Viruses; Endocrinopathy; Human; Picornaviridae; Diabetes mellitus; Langerhans islet; Enterovirus; In vitro; Enterovirus ·Coxsackievirus ·Echovirus; Virus; Infection; In vivo; Receptors; Poliovirus Human pancreas Islets ·Beta cells; Endocrine pancreas; Biological receptor
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-003-1297-z

It is thought that enterovirus infections cause beta-cell damage and contribute to the development of Type 1 diabetes by replicating in the pancreatic islets. We sought evidence for this through autopsy studies and by investigating known enterovirus receptors in cultured human islets.
Autopsy pancreases from 12 newborn infants who died of fulminant coxsackievirus infections and from 65 Type 1 diabetic patients were studied for presence of enteroviral ribonucleic acid by in situ hybridisation. Forty non-diabetic control pancreases were included in the study. The expression and role of receptor candidates in cultured human islets were investigated with receptor-specific antibodies using immunocytochemistry and functional assays.
Enterovirus-positive islet cells were found in some of both autopsy specimen collections, but not in control pancreases. No infected cells were seen in exocrine tissue. The cell surface molecules, poliovirus receptor and integrin alphavbeta3, which act as enterovirus receptors in established cell lines, were expressed in beta cells. Antibodies to poliovirus receptor, human coxsackievirus and adenovirus receptor and integrin alphavbeta3 protected islets and beta cells from adverse effects of poliovirus, coxsackie B viruses, and several of the arginine-glycine-aspartic acid motifs containing enteroviruses and human parechovirus 1 respectively. No evidence was found for expression of the decay-accelerating factor which acts as a receptor for several islet-cell-replicating echoviruses in established cell lines.
The results show a definite islet-cell tropism of enteroviruses in the human pancreas. Some enteroviruses seem to use previously identified cell surface molecules as receptors in beta cells, whereas the identity of receptors used by other enteroviruses remains unknown.