The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output.

To develop more detailed models of EBV persistence we have studied the dynamics of virus shedding in healthy carriers. We demonstrate that EBV shedding into saliva is continuous and rapid such that the virus level is replaced in < or =2 minutes, the average time that a normal individual swallows....

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Main Authors: Vey Hadinoto, Michael Shapiro, Chia Chi Sun, David A Thorley-Lawson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-07-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC2698984?pdf=render
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spelling doaj-5ee303e5c21f49d1b825530203199c8c2020-11-25T00:12:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742009-07-0157e100049610.1371/journal.ppat.1000496The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output.Vey HadinotoMichael ShapiroChia Chi SunDavid A Thorley-LawsonTo develop more detailed models of EBV persistence we have studied the dynamics of virus shedding in healthy carriers. We demonstrate that EBV shedding into saliva is continuous and rapid such that the virus level is replaced in < or =2 minutes, the average time that a normal individual swallows. Thus, the mouth is not a reservoir of virus but a conduit through which a continuous flow stream of virus passes in saliva. Consequently, virus is being shed at a much higher rate than previously thought, a level too high to be accounted for by replication in B cells in Waldeyer's ring alone. Virus shedding is relatively stable over short periods (hours-days) but varies through 3.5 to 5.5 logs over longer periods, a degree of variation that also cannot be accounted for solely by replication in B cells. This variation means, contrary to what is generally believed, that the definition of high and low shedder is not so much a function of variation between individuals but within individuals over time. The dynamics of shedding describe a process governing virus production that is occurring independently < or =3 times at any moment. This process grows exponentially and is then randomly terminated. We propose that these dynamics are best explained by a model where single B cells sporadically release virus that infects anywhere from 1 to 5 epithelial cells. This infection spreads at a constant exponential rate and is terminated randomly, resulting in infected plaques of epithelial cells ranging in size from 1 to 10(5) cells. At any one time there are a very small number (< or =3) of plaques. We suggest that the final size of these plaques is a function of the rate of infectious spread within the lymphoepithelium which may be governed by the structural complexity of the tissue but is ultimately limited by the immune response.http://europepmc.org/articles/PMC2698984?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Vey Hadinoto
Michael Shapiro
Chia Chi Sun
David A Thorley-Lawson
spellingShingle Vey Hadinoto
Michael Shapiro
Chia Chi Sun
David A Thorley-Lawson
The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output.
PLoS Pathogens
author_facet Vey Hadinoto
Michael Shapiro
Chia Chi Sun
David A Thorley-Lawson
author_sort Vey Hadinoto
title The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output.
title_short The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output.
title_full The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output.
title_fullStr The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output.
title_full_unstemmed The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output.
title_sort dynamics of ebv shedding implicate a central role for epithelial cells in amplifying viral output.
publisher Public Library of Science (PLoS)
series PLoS Pathogens
issn 1553-7366
1553-7374
publishDate 2009-07-01
description To develop more detailed models of EBV persistence we have studied the dynamics of virus shedding in healthy carriers. We demonstrate that EBV shedding into saliva is continuous and rapid such that the virus level is replaced in < or =2 minutes, the average time that a normal individual swallows. Thus, the mouth is not a reservoir of virus but a conduit through which a continuous flow stream of virus passes in saliva. Consequently, virus is being shed at a much higher rate than previously thought, a level too high to be accounted for by replication in B cells in Waldeyer's ring alone. Virus shedding is relatively stable over short periods (hours-days) but varies through 3.5 to 5.5 logs over longer periods, a degree of variation that also cannot be accounted for solely by replication in B cells. This variation means, contrary to what is generally believed, that the definition of high and low shedder is not so much a function of variation between individuals but within individuals over time. The dynamics of shedding describe a process governing virus production that is occurring independently < or =3 times at any moment. This process grows exponentially and is then randomly terminated. We propose that these dynamics are best explained by a model where single B cells sporadically release virus that infects anywhere from 1 to 5 epithelial cells. This infection spreads at a constant exponential rate and is terminated randomly, resulting in infected plaques of epithelial cells ranging in size from 1 to 10(5) cells. At any one time there are a very small number (< or =3) of plaques. We suggest that the final size of these plaques is a function of the rate of infectious spread within the lymphoepithelium which may be governed by the structural complexity of the tissue but is ultimately limited by the immune response.
url http://europepmc.org/articles/PMC2698984?pdf=render
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