Echovirus 6 Infects Human Exocrine and Endocrine Pancreatic Cells and Induces Pro-Inflammatory Innate Immune Response.
Human enteroviruses (HEV), especially coxsackievirus serotype B (CVB) and echovirus (E), have been associated with diseases of both the exocrine and endocrine pancreas, but so far evidence on HEV infection in human pancreas has been reported only in islets and ductal cells. This study aimed to investigate the capability of echovirus strains to infect human exocrine and endocrine pancreatic cells. Infection of explanted human islets and exocrine cells with seven field strains of E6 caused cytopathic effect, virus titer increase and production of HEV protein VP1 in both cell types. Virus particles were found in islets and acinar cells infected with E6. No cytopathic effect or infectious progeny production was observed in exocrine cells exposed to the beta cell-tropic strains of E16 and E30. Endocrine cells responded to E6, E16 and E30 by upregulating the transcription of interferon-induced with helicase C domain 1 (IF1H1), 2'-5'-oligoadenylate synthetase 1 (OAS1), interferon-β (IFN-β), chemokine (C-X-C motif) ligand 10 (CXCL10) and chemokine (C-C motif) ligand 5 (CCL5). Echovirus 6, but not E16 or E30, led to increased transcription of these genes in exocrine cells. These data demonstrate for the first time that human exocrine cells represent a target for E6 infection and suggest that certain HEV serotypes can replicate in human pancreatic exocrine cells, while the pancreatic endocrine cells are permissive to a wider range of HEV.
Cellular Autoimmunity Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Jan Waldenströms gata 35, CRC 91:10 205 02 Malmö, Sweden. luis.sarmiento-perez@med.lu.se.
Luis
L
Sarmiento
Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, 75185 Uppsala, Sweden. gun.ergida.frisk@gmail.com.
Gun
G
Frisk
Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, 75185 Uppsala, Sweden. mahesh.anagandla@gmail.com.
Mahesh
M
Anagandula
Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, 75185 Uppsala, Sweden. monika80hodik@gmail.com.
Monika
M
Hodik
Cellular Autoimmunity Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Jan Waldenströms gata 35, CRC 91:10 205 02 Malmö, Sweden. ilariabarchetta@hotmail.com.|Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, 00185 Rome, Italy. ilariabarchetta@hotmail.com.
Ilaria
I
Barchetta
Cellular Autoimmunity Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Jan Waldenströms gata 35, CRC 91:10 205 02 Malmö, Sweden. eitan.netanyah@med.lu.se.
Eitan
E
Netanyah
Department of Immunology and Genetics on Diabetes, National Institute of Endocrinology, 10400 Havana, Cuba. diabetes@infomed.sld.cu.
Eduardo
E
Cabrera-Rode
Cellular Autoimmunity Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Jan Waldenströms gata 35, CRC 91:10 205 02 Malmö, Sweden. corrado.cilio@med.lu.se.
Corrado M
CM
Cilio
D003588:Cytopathogenic Effect, Viral; D004458:Echovirus 6, Human / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000276:immunology* / Q000821:virology*; D009924:Organ Culture Techniques; D046790:Pancreas, Exocrine / Q000276:immunology* / Q000821:virology*; D019562:Viral Load; D015678:Viral Structural Proteins / Q000032:analysis
D007155:Immunologic Factors; D015678:Viral Structural Proteins
acinar cells; echovirus; enterovirus; inflammation; islet of Langerhans; pancreas; tropism