Viral kinetics suggests a reconciliation of the disparate observations of the modulation of claudin-1 expression on cells exposed to hepatitis C virus

Padmanabhan, Pranesh and Dixit, Narendra M. (2012) Viral kinetics suggests a reconciliation of the disparate observations of the modulation of claudin-1 expression on cells exposed to hepatitis C virus. PLoS One, 7 4: e36107-e36107. doi:10.1371/journal.pone.0036107


Author Padmanabhan, Pranesh
Dixit, Narendra M.
Title Viral kinetics suggests a reconciliation of the disparate observations of the modulation of claudin-1 expression on cells exposed to hepatitis C virus
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-04-24
Sub-type Article (original research)
DOI 10.1371/journal.pone.0036107
Open Access Status DOI
Volume 7
Issue 4
Start page e36107
End page e36107
Total pages 7
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Abstract The tight junction protein claudin-1 (CLDN1) is necessary for hepatitis C virus (HCV) entry into target cells. Recent studies have made disparate observations of the modulation of the expression of CLDN1 on cells following infection by HCV. In one study, the mean CLDN1 expression on cells exposed to HCV declined, whereas in another study HCV infected cells showed increased CLDN1 expression compared to uninfected cells. Consequently, the role of HCV in modulating CLDN1 expression, and hence the frequency of cellular superinfection, remains unclear. Here, we present a possible reconciliation of these disparate observations. We hypothesized that viral kinetics and not necessarily HCV-induced receptor modulation underlies these disparate observations. To test this hypothesis, we constructed a mathematical model of viral kinetics in vitro that mimicked the above experiments. Model predictions provided good fits to the observed evolution of the distribution of CLDN1 expression on cells following exposure to HCV. Cells with higher CLDN1 expression were preferentially infected and outgrown by cells with lower CLDN1 expression, resulting in a decline of the mean CLDN1 expression with time. At the same time, because the susceptibility of cells to infection increased with CLDN1 expression, infected cells tended to have higher CLDN1 expression on average than uninfected cells. Our study thus presents an explanation of the disparate observations of CLDN1 expression following HCV infection and points to the importance of considering viral kinetics in future studies of receptor expression on cells exposed to HCV.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Sat, 13 Jun 2015, 12:16:52 EST by Pranesh Padmanabhan on behalf of Queensland Brain Institute