T-Cell Tropism of Simian Varicella Virus during Primary Infection

Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and im...

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Main Authors: Ouwendijk, Werner J. D., Mahalingam, Ravi, de Swart, Rik L., Haagmans, Bart L., van Amerongen, Geert, Getu, Sarah, Gilden, Don, Osterhaus, Albert D. M. E., Verjans, Georges M. G. M.
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649965/
id pubmed-3649965
recordtype oai_dc
spelling pubmed-36499652013-05-14 T-Cell Tropism of Simian Varicella Virus during Primary Infection Ouwendijk, Werner J. D. Mahalingam, Ravi de Swart, Rik L. Haagmans, Bart L. van Amerongen, Geert Getu, Sarah Gilden, Don Osterhaus, Albert D. M. E. Verjans, Georges M. G. M. Research Article Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, SVV was found primarily in neurons and occasionally in memory T-cells adjacent to neurons. In conclusion, the data suggest the role of memory T-cells in disseminating SVV to its target organs during primary infection of its natural and immunocompetent host. Public Library of Science 2013-05-09 /pmc/articles/PMC3649965/ /pubmed/23675304 http://dx.doi.org/10.1371/journal.ppat.1003368 Text en © 2013 Ouwendijk et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ouwendijk, Werner J. D.
Mahalingam, Ravi
de Swart, Rik L.
Haagmans, Bart L.
van Amerongen, Geert
Getu, Sarah
Gilden, Don
Osterhaus, Albert D. M. E.
Verjans, Georges M. G. M.
spellingShingle Ouwendijk, Werner J. D.
Mahalingam, Ravi
de Swart, Rik L.
Haagmans, Bart L.
van Amerongen, Geert
Getu, Sarah
Gilden, Don
Osterhaus, Albert D. M. E.
Verjans, Georges M. G. M.
T-Cell Tropism of Simian Varicella Virus during Primary Infection
author_facet Ouwendijk, Werner J. D.
Mahalingam, Ravi
de Swart, Rik L.
Haagmans, Bart L.
van Amerongen, Geert
Getu, Sarah
Gilden, Don
Osterhaus, Albert D. M. E.
Verjans, Georges M. G. M.
author_sort Ouwendijk, Werner J. D.
title T-Cell Tropism of Simian Varicella Virus during Primary Infection
title_short T-Cell Tropism of Simian Varicella Virus during Primary Infection
title_full T-Cell Tropism of Simian Varicella Virus during Primary Infection
title_fullStr T-Cell Tropism of Simian Varicella Virus during Primary Infection
title_full_unstemmed T-Cell Tropism of Simian Varicella Virus during Primary Infection
title_sort t-cell tropism of simian varicella virus during primary infection
description Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, SVV was found primarily in neurons and occasionally in memory T-cells adjacent to neurons. In conclusion, the data suggest the role of memory T-cells in disseminating SVV to its target organs during primary infection of its natural and immunocompetent host.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649965/
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