PMID- 29367250 OWN - NLM STAT- MEDLINE DCOM- 20180417 LR - 20181202 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 92 IP - 7 DP - 2018 Apr 1 TI - Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells. LID - 10.1128/JVI.00026-18 [doi] LID - e00026-18 AB - Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells.IMPORTANCE The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41 infection on human enterochromaffin cells and found it stimulates serotonin secretion in the cells, which is involved in regulation of intestinal secretion and gut motility and can also activate enteric glia cells, which are found in close proximity to enterochromaffin cells in vivo This disruption of gut barrier homeostasis as maintained by these cells following human adenovirus 41 infection might be a mechanism in enteric adenovirus pathogenesis in humans and could indicate a possible serotonin-dependent cross talk between human adenovirus 41, enterochromaffin cells, and enteric glia cells. CI - Copyright (c) 2018 American Society for Microbiology. FAU - Westerberg, Sonja AU - Westerberg S AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Hagbom, Marie AU - Hagbom M AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Rajan, Anandi AU - Rajan A AD - Department of Clinical Microbiology, Division of Virology, and Molecular Infection Medicine Sweden, Umea University, Umea, Sweden. FAU - Loitto, Vesa AU - Loitto V AD - Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Persson, B David AU - Persson BD AD - Department of Clinical Microbiology, Division of Virology, and Molecular Infection Medicine Sweden, Umea University, Umea, Sweden. FAU - Allard, Annika AU - Allard A AD - Department of Clinical Microbiology, Division of Virology, and Molecular Infection Medicine Sweden, Umea University, Umea, Sweden. FAU - Nordgren, Johan AU - Nordgren J AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Sharma, Sumit AU - Sharma S AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Magnusson, Karl-Eric AU - Magnusson KE AD - Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Arnberg, Niklas AU - Arnberg N AD - Department of Clinical Microbiology, Division of Virology, and Molecular Infection Medicine Sweden, Umea University, Umea, Sweden. FAU - Svensson, Lennart AU - Svensson L AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden lennart.t.svensson@liu.se. AD - Department of Medicine, Karolinska Institute, Stockholm, Sweden. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180314 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Coxsackie and Adenovirus Receptor-Like Membrane Protein) RN - 0 (Glial Fibrillary Acidic Protein) RN - 333DO1RDJY (Serotonin) SB - IM MH - A549 Cells MH - Adenoviridae/*metabolism MH - Adenoviridae Infections/*metabolism/pathology MH - Coxsackie and Adenovirus Receptor-Like Membrane Protein/metabolism MH - Enterochromaffin Cells/*metabolism/pathology/virology MH - Glial Fibrillary Acidic Protein/metabolism MH - Humans MH - Neuroglia/*metabolism/pathology/virology MH - Serotonin/*metabolism PMC - PMC5972892 OTO - NOTNLM OT - EC cells OT - enteric adenovirus OT - enteric glia cells OT - gastroenteritis OT - serotonin EDAT- 2018/01/26 06:00 MHDA- 2018/04/18 06:00 PMCR- 2018/09/14 CRDT- 2018/01/26 06:00 PHST- 2018/01/09 00:00 [received] PHST- 2018/01/09 00:00 [accepted] PHST- 2018/01/26 06:00 [pubmed] PHST- 2018/04/18 06:00 [medline] PHST- 2018/01/26 06:00 [entrez] PHST- 2018/09/14 00:00 [pmc-release] AID - JVI.00026-18 [pii] AID - 00026-18 [pii] AID - 10.1128/JVI.00026-18 [doi] PST - epublish SO - J Virol. 2018 Mar 14;92(7):e00026-18. doi: 10.1128/JVI.00026-18. Print 2018 Apr 1.