Echovirus 6 Infects Human Exocrine and Endocrine Pancreatic Cells and Induces Pro-Inflammatory Innate Immune Response

Abstract

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.

Vitamin D status, enterovirus infection, and type 1 diabetes in Italian children/adolescents

“…T1D is an immune‐mediated disease due to the merging of genetic susceptibility with exogenous beta cell stressors and the consequent activation of an immune response to beta cell‐specific antigens that perpetuate the insult . Among environmental factors, EVs are widespread viral agents that cause common infections worldwide and that are able to hit the human pancreas, particularly beta cells . The results from our group, Scandinavian investigators, clinicians, and pathologists, indicate persistent EV infections as a major triggering factor for T1D.…”

Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway

“…The CD8 + T cell bias and the known susceptibility of the human pancreas to multiple common viruses, including cytomegalovirus, enteroviruses, Epstein-Barr virus, and hepatitis (Alidjinou et al, 2017; Chan et al, 2014; Rawla et al, 2017; Sarmiento et al, 2017), suggests that pancreas TRMs may originate from antiviral immune responses. In this way, TRMs could be important for rapid in situ clearance of viruses with pancreatic tropism.…”

Immune Transcriptome of Cells Infected with Enterovirus Strains Obtained from Cases of Autoimmune Thyroid Disease

“…Successively, part of them seroconverted to diabetes-related autoantibodies or progressed directly to autoimmune diabetes. Thus, in vitro studies of virally infected islets support the contention that pancreatic autoimmunity derives from the ability of particular viral strains to modulate gene expression in islet cells and to activate innate immunity factors implicated in organ-specific autoimmunity [ 29 ].…”