Simian Varicella Virus Infects Enteric Neurons and α4β7 Integrin-Expressing Gut-Tropic T-Cells in Nonhuman Primates
The pathogenesis of enteric zoster, a rare debilitating complication of reactivation of latent varicella-zoster virus (VZV) in the enteric nervous system (ENS), is largely unknown. Infection of monkeys with the closely related Varicellovirus simian varicella virus (SVV) mimics VZV disease in humans....
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| Format: | Article |
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MDPI AG
2018-03-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/10/4/156 |
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| author | Werner J. D. Ouwendijk Suzanne van Veen Tamana Mehraban Ravi Mahalingam Georges M. G. M. Verjans |
| author_facet | Werner J. D. Ouwendijk Suzanne van Veen Tamana Mehraban Ravi Mahalingam Georges M. G. M. Verjans |
| author_sort | Werner J. D. Ouwendijk |
| collection | DOAJ |
| description | The pathogenesis of enteric zoster, a rare debilitating complication of reactivation of latent varicella-zoster virus (VZV) in the enteric nervous system (ENS), is largely unknown. Infection of monkeys with the closely related Varicellovirus simian varicella virus (SVV) mimics VZV disease in humans. In this study, we determined the applicability of the SVV nonhuman primate model to study Varicellovirus infection of the ENS. We confirmed VZV infection of the gut in latently infected adults and demonstrated that SVV DNA was similarly present in gut of monkeys latently infected with SVV using quantitative real-time PCR. In situ analyses showed that enteric neurons expressed SVV open reading frame (ORF) 63 RNA, but not viral nucleocapsid proteins, suggestive of latent ENS infection. During primary infection, SVV-infected T-cells were detected in gut-draining mesenteric lymph nodes and located in close vicinity to enteric nerves in the gut. Furthermore, flow cytometric analysis of blood from acutely SVV-infected monkeys demonstrated that virus-infected T-cells expressed the gut-homing receptor α4β7 integrin. Collectively, the data demonstrate that SVV infects ENS neurons during primary infection and supports the role of T-cells in virus dissemination to the gut. Because SVV reactivation can be experimentally induced, the SVV nonhuman primate model holds great potential to study the pathogenesis of enteric zoster. |
| first_indexed | 2024-12-10T23:04:42Z |
| format | Article |
| id | doaj.art-692e91fdc7644192a03d8779e9e540a2 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-10T23:04:42Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-692e91fdc7644192a03d8779e9e540a22022-12-22T01:30:04ZengMDPI AGViruses1999-49152018-03-0110415610.3390/v10040156v10040156Simian Varicella Virus Infects Enteric Neurons and α4β7 Integrin-Expressing Gut-Tropic T-Cells in Nonhuman PrimatesWerner J. D. Ouwendijk0Suzanne van Veen1Tamana Mehraban2Ravi Mahalingam3Georges M. G. M. Verjans4Department of Viroscience, Erasmus MC, 3015 CE Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus MC, 3015 CE Rotterdam, The NetherlandsDepartment of Viroscience, Erasmus MC, 3015 CE Rotterdam, The NetherlandsDepartment of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Viroscience, Erasmus MC, 3015 CE Rotterdam, The NetherlandsThe pathogenesis of enteric zoster, a rare debilitating complication of reactivation of latent varicella-zoster virus (VZV) in the enteric nervous system (ENS), is largely unknown. Infection of monkeys with the closely related Varicellovirus simian varicella virus (SVV) mimics VZV disease in humans. In this study, we determined the applicability of the SVV nonhuman primate model to study Varicellovirus infection of the ENS. We confirmed VZV infection of the gut in latently infected adults and demonstrated that SVV DNA was similarly present in gut of monkeys latently infected with SVV using quantitative real-time PCR. In situ analyses showed that enteric neurons expressed SVV open reading frame (ORF) 63 RNA, but not viral nucleocapsid proteins, suggestive of latent ENS infection. During primary infection, SVV-infected T-cells were detected in gut-draining mesenteric lymph nodes and located in close vicinity to enteric nerves in the gut. Furthermore, flow cytometric analysis of blood from acutely SVV-infected monkeys demonstrated that virus-infected T-cells expressed the gut-homing receptor α4β7 integrin. Collectively, the data demonstrate that SVV infects ENS neurons during primary infection and supports the role of T-cells in virus dissemination to the gut. Because SVV reactivation can be experimentally induced, the SVV nonhuman primate model holds great potential to study the pathogenesis of enteric zoster.http://www.mdpi.com/1999-4915/10/4/156varicella-zoster virussimian varicella virusenteric nervous systemnonhuman primateT-cells |
| spellingShingle | Werner J. D. Ouwendijk Suzanne van Veen Tamana Mehraban Ravi Mahalingam Georges M. G. M. Verjans Simian Varicella Virus Infects Enteric Neurons and α4β7 Integrin-Expressing Gut-Tropic T-Cells in Nonhuman Primates Viruses varicella-zoster virus simian varicella virus enteric nervous system nonhuman primate T-cells |
| title | Simian Varicella Virus Infects Enteric Neurons and α4β7 Integrin-Expressing Gut-Tropic T-Cells in Nonhuman Primates |
| title_full | Simian Varicella Virus Infects Enteric Neurons and α4β7 Integrin-Expressing Gut-Tropic T-Cells in Nonhuman Primates |
| title_fullStr | Simian Varicella Virus Infects Enteric Neurons and α4β7 Integrin-Expressing Gut-Tropic T-Cells in Nonhuman Primates |
| title_full_unstemmed | Simian Varicella Virus Infects Enteric Neurons and α4β7 Integrin-Expressing Gut-Tropic T-Cells in Nonhuman Primates |
| title_short | Simian Varicella Virus Infects Enteric Neurons and α4β7 Integrin-Expressing Gut-Tropic T-Cells in Nonhuman Primates |
| title_sort | simian varicella virus infects enteric neurons and α4β7 integrin expressing gut tropic t cells in nonhuman primates |
| topic | varicella-zoster virus simian varicella virus enteric nervous system nonhuman primate T-cells |
| url | http://www.mdpi.com/1999-4915/10/4/156 |
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