Vectorial entry and release of hepatitis a virus in polarized human hepatocytes

Snooks, Michelle J., Bhat, Purnima, Mackenzie, Jason, Counihan, Natalie A., Vaughan, Nicola and Anderson, David A. (2008) Vectorial entry and release of hepatitis a virus in polarized human hepatocytes. Journal of Virology, 82 17: 8733-8742. doi:10.1128/JVI.00219-08

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Author Snooks, Michelle J.
Bhat, Purnima
Mackenzie, Jason
Counihan, Natalie A.
Vaughan, Nicola
Anderson, David A.
Title Vectorial entry and release of hepatitis a virus in polarized human hepatocytes
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 2008-09-01
Year available 2008
Sub-type Article (original research)
DOI 10.1128/JVI.00219-08
Open Access Status File (Publisher version)
Volume 82
Issue 17
Start page 8733
End page 8742
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society of Microbiology
Collection year 2009
Language eng
Subject C1
060602 Animal Physiology - Cell
920109 Infectious Diseases
Abstract Hepatitis A virus (HAV) is an enterically transmitted virus that replicates predominantly in hepatocytes within the liver before excretion via bile through feces. Hepatocytes are polarized epithelial cells, and it has been assumed that the virus load in bile results from direct export of RAV via the apical domain of polarized hepatocytes. We have developed a subclone of hepatocyte-derived HepG2 cells (clone N6) that maintains functional characteristics of polarized hepatocytes but displays morphology typical of columnar epithelial cells, rather than the complex morphology that is typical of hepatocytes. N6 cells form microcolonies of polarized cells when grown on glass and confluent monolayers of polarized cells on semipermeable membranes. When N6 microcolonies were exposed to HAV, infection was restricted to peripheral cells of polarized colonies, whereas all cells could be infected in colonies of nonpolarized HepG2 cells (clone C11) or following disruption of tight junctions in N6 colonies with EGTA. This suggests that viral entry occurs predominantly via the basolateral plasma membrane, consistent with uptake of virus from the bloodstream after enteric exposure, as expected. Viral export was also found to be markedly vectorial in N6 but not C11 cells. However, rather than being exported from the apical domain as expected, more than 95% of HAV was exported via the basolateral domain of N6 cells, suggesting that virus is first excreted from infected hepatocytes into the bloodstream rather than to the biliary tree. Enteric excretion of HAV may therefore rely on reuptake and transcytosis of progeny HAV across hepatocytes into the bile. These studies provide the first example of the interactions between viruses and polarized hepatocytes.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
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Created: Wed, 18 Mar 2009, 12:03:42 EST