Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro.
Analysis of enterovirus infection is difficult in animals because they express different virus receptors than humans, and static cell culture systems do not reproduce the physical complexity of the human intestinal epithelium. Here, using coxsackievirus B1 (CVB1) as a prototype enterovirus strain, w...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0169412&type=printable |
| _version_ | 1826579320013848576 |
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| author | Remi Villenave Samantha Q Wales Tiama Hamkins-Indik Efstathia Papafragkou James C Weaver Thomas C Ferrante Anthony Bahinski Christopher A Elkins Michael Kulka Donald E Ingber |
| author_facet | Remi Villenave Samantha Q Wales Tiama Hamkins-Indik Efstathia Papafragkou James C Weaver Thomas C Ferrante Anthony Bahinski Christopher A Elkins Michael Kulka Donald E Ingber |
| author_sort | Remi Villenave |
| collection | DOAJ |
| description | Analysis of enterovirus infection is difficult in animals because they express different virus receptors than humans, and static cell culture systems do not reproduce the physical complexity of the human intestinal epithelium. Here, using coxsackievirus B1 (CVB1) as a prototype enterovirus strain, we demonstrate that human enterovirus infection, replication and infectious virus production can be analyzed in vitro in a human Gut-on-a-Chip microfluidic device that supports culture of highly differentiated human villus intestinal epithelium under conditions of fluid flow and peristalsis-like motions. When CVB1 was introduced into the epithelium-lined intestinal lumen of the device, virions entered the epithelium, replicated inside the cells producing detectable cytopathic effects (CPEs), and both infectious virions and inflammatory cytokines were released in a polarized manner from the cell apex, as they could be detected in the effluent from the epithelial microchannel. When the virus was introduced via a basal route of infection (by inoculating virus into fluid flowing through a parallel lower 'vascular' channel separated from the epithelial channel by a porous membrane), significantly lower viral titers, decreased CPEs, and delayed caspase-3 activation were observed; however, cytokines continued to be secreted apically. The presence of continuous fluid flow through the epithelial lumen also resulted in production of a gradient of CPEs consistent with the flow direction. Thus, the human Gut-on-a-Chip may provide a suitable in vitro model for enteric virus infection and for investigating mechanisms of enterovirus pathogenesis. |
| first_indexed | 2024-12-19T08:10:51Z |
| format | Article |
| id | doaj.art-81c1e3f16dda46bfb689119331286832 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T14:16:24Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-81c1e3f16dda46bfb6891193312868322025-02-27T05:33:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e016941210.1371/journal.pone.0169412Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro.Remi VillenaveSamantha Q WalesTiama Hamkins-IndikEfstathia PapafragkouJames C WeaverThomas C FerranteAnthony BahinskiChristopher A ElkinsMichael KulkaDonald E IngberAnalysis of enterovirus infection is difficult in animals because they express different virus receptors than humans, and static cell culture systems do not reproduce the physical complexity of the human intestinal epithelium. Here, using coxsackievirus B1 (CVB1) as a prototype enterovirus strain, we demonstrate that human enterovirus infection, replication and infectious virus production can be analyzed in vitro in a human Gut-on-a-Chip microfluidic device that supports culture of highly differentiated human villus intestinal epithelium under conditions of fluid flow and peristalsis-like motions. When CVB1 was introduced into the epithelium-lined intestinal lumen of the device, virions entered the epithelium, replicated inside the cells producing detectable cytopathic effects (CPEs), and both infectious virions and inflammatory cytokines were released in a polarized manner from the cell apex, as they could be detected in the effluent from the epithelial microchannel. When the virus was introduced via a basal route of infection (by inoculating virus into fluid flowing through a parallel lower 'vascular' channel separated from the epithelial channel by a porous membrane), significantly lower viral titers, decreased CPEs, and delayed caspase-3 activation were observed; however, cytokines continued to be secreted apically. The presence of continuous fluid flow through the epithelial lumen also resulted in production of a gradient of CPEs consistent with the flow direction. Thus, the human Gut-on-a-Chip may provide a suitable in vitro model for enteric virus infection and for investigating mechanisms of enterovirus pathogenesis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0169412&type=printable |
| spellingShingle | Remi Villenave Samantha Q Wales Tiama Hamkins-Indik Efstathia Papafragkou James C Weaver Thomas C Ferrante Anthony Bahinski Christopher A Elkins Michael Kulka Donald E Ingber Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro. PLoS ONE |
| title | Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro. |
| title_full | Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro. |
| title_fullStr | Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro. |
| title_full_unstemmed | Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro. |
| title_short | Human Gut-On-A-Chip Supports Polarized Infection of Coxsackie B1 Virus In Vitro. |
| title_sort | human gut on a chip supports polarized infection of coxsackie b1 virus in vitro |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0169412&type=printable |
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