The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry

<p>Abstract</p> <p>Background</p> <p>Three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, sev...

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Main Authors: Rubinstein Eric, Lecoeur Cécile, Potel Julie, Pillez André, Canton Jonathan, Delgrange David, Lavie Muriel, Rocha-Perugini Vera, Dubuisson Jean, Wychowski Czeslaw, Cocquerel Laurence
Format: Article
Language:English
Published: BMC 2009-05-01
Series:BMC Microbiology
Online Access:http://www.biomedcentral.com/1471-2180/9/111
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author Rubinstein Eric
Lecoeur Cécile
Potel Julie
Pillez André
Canton Jonathan
Delgrange David
Lavie Muriel
Rocha-Perugini Vera
Dubuisson Jean
Wychowski Czeslaw
Cocquerel Laurence
author_facet Rubinstein Eric
Lecoeur Cécile
Potel Julie
Pillez André
Canton Jonathan
Delgrange David
Lavie Muriel
Rocha-Perugini Vera
Dubuisson Jean
Wychowski Czeslaw
Cocquerel Laurence
author_sort Rubinstein Eric
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Interestingly, CD81 is also required for <it>Plasmodium </it>infection. A major characteristic of tetraspanins is their ability to interact with each other and other transmembrane proteins to build tetraspanin-enriched microdomains (TEM).</p> <p>Results</p> <p>In our study, we describe a human hepatoma Huh-7 cell clone (Huh-7w7) which has lost CD81 expression and can be infected by HCV when human CD81 (hCD81) or mouse CD81 (mCD81) is ectopically expressed. We took advantage of these permissive cells expressing mCD81 and the previously described MT81/MT81w mAbs to analyze the role of TEM-associated CD81 in HCV infection. Importantly, MT81w antibody, which only recognizes TEM-associated mCD81, did not strongly affect HCV infection. Furthermore, cholesterol depletion, which inhibits HCV infection and reduces total cell surface expression of CD81, did not affect TEM-associated CD81 levels. In addition, sphingomyelinase treatment, which also reduces HCV infection and cell surface expression of total CD81, raised TEM-associated CD81 levels.</p> <p>Conclusion</p> <p>In contrast to <it>Plasmodium </it>infection, our data show that association of CD81 with TEM is not essential for the early steps of HCV life cycle, indicating that these two pathogens, while using the same molecules, invade their host by different mechanisms.</p>
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spelling doaj.art-9a460d7c5da24c0da568f46b1d50edb92022-12-21T23:27:23ZengBMCBMC Microbiology1471-21802009-05-019111110.1186/1471-2180-9-111The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entryRubinstein EricLecoeur CécilePotel JuliePillez AndréCanton JonathanDelgrange DavidLavie MurielRocha-Perugini VeraDubuisson JeanWychowski CzeslawCocquerel Laurence<p>Abstract</p> <p>Background</p> <p>Three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Interestingly, CD81 is also required for <it>Plasmodium </it>infection. A major characteristic of tetraspanins is their ability to interact with each other and other transmembrane proteins to build tetraspanin-enriched microdomains (TEM).</p> <p>Results</p> <p>In our study, we describe a human hepatoma Huh-7 cell clone (Huh-7w7) which has lost CD81 expression and can be infected by HCV when human CD81 (hCD81) or mouse CD81 (mCD81) is ectopically expressed. We took advantage of these permissive cells expressing mCD81 and the previously described MT81/MT81w mAbs to analyze the role of TEM-associated CD81 in HCV infection. Importantly, MT81w antibody, which only recognizes TEM-associated mCD81, did not strongly affect HCV infection. Furthermore, cholesterol depletion, which inhibits HCV infection and reduces total cell surface expression of CD81, did not affect TEM-associated CD81 levels. In addition, sphingomyelinase treatment, which also reduces HCV infection and cell surface expression of total CD81, raised TEM-associated CD81 levels.</p> <p>Conclusion</p> <p>In contrast to <it>Plasmodium </it>infection, our data show that association of CD81 with TEM is not essential for the early steps of HCV life cycle, indicating that these two pathogens, while using the same molecules, invade their host by different mechanisms.</p>http://www.biomedcentral.com/1471-2180/9/111
spellingShingle Rubinstein Eric
Lecoeur Cécile
Potel Julie
Pillez André
Canton Jonathan
Delgrange David
Lavie Muriel
Rocha-Perugini Vera
Dubuisson Jean
Wychowski Czeslaw
Cocquerel Laurence
The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry
BMC Microbiology
title The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry
title_full The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry
title_fullStr The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry
title_full_unstemmed The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry
title_short The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry
title_sort association of cd81 with tetraspanin enriched microdomains is not essential for hepatitis c virus entry
url http://www.biomedcentral.com/1471-2180/9/111
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