AustralieFrV1, Main, Exploration, bibRecord, 004F14

Hepatitis C Virus Envelope Glycoprotein Signatures Are Associated With Treatment Failure and Modulation of Viral Entry and Neutralization

Identifieur interne : 004F14 ( Main/Exploration ); précédent : 004F13; suivant : 004F15

Hepatitis C Virus Envelope Glycoprotein Signatures Are Associated With Treatment Failure and Modulation of Viral Entry and Neutralization

Auteurs : Evelyne Schvoerer [France] ; Rémy Moenne-Loccoz [France] ; John M. Murray [Australie] ; Aurélie Velar [France] ; Marine Turek [France] ; Isabel Fofana [France] ; Samira Fafi-Kremer [France] ; Anne-Claire Erba [France] ; François Habersetzer [France] ; Michel Doffoël [France] ; Jean-Pierre Gut [France] ; Maureen J. Donlin [États-Unis] ; John E. Tavis [États-Unis] ; Mirjam B. Zeisel [France] ; Françoise Stoll-Keller [France] ; Thomas F. Baumert [France]

Source :

The Journal of infectious diseases [ 0022-1899 ] ; 2013.

RBID : Pascal:13-0149646

Descripteurs français

Pascal (Inist)
- Virus hépatite C, Glycoprotéine, Traitement, Echec, Neutralisation, Infection.

English descriptors

KwdEn :
- Failure, Glycoprotein, Hepatitis C virus, Infection, Neutralization, Treatment.

Abstract

Background. A major challenge for antiviral treatment of hepatitis C virus (HCV) infection is viral resistance, potentially resulting from the high variability of HCV envelope glycoproteins and subsequent selection of strains with enhanced infectivity and/or immune escape. Methods. We used a bioinformatics and functional approach to investigate whether E1/E2 envelope glycoprotein structure and function were associated with treatment failure in 92 patients infected with HCV genotype 1. Results. Bioinformatics analysis identified 1 sustain virological response (R)-related residue in E1 (219T) and 2 non-SVR (NR)-related molecular signatures in E2 (431A and 642V) in HCV genotype 1a. Two of these positions also appeared in minimal networks separating NR patients from R patients. HCV pseudoparticles (HCVpp) expressing 431A and 642V resulted in a decrease in antibody-mediated neutralization by pretreatment sera. 431A/ HCVpp entry into Huh7.5 cells increased with overexpression of CD81 and SR-BI. Moreover, an association of envelope glycoprotein signatures with treatment failure was confirmed in an independent cohort (Virahep-C). Conclusions. Combined in silico and functional analyses demonstrate that envelope glycoprotein signatures associated with treatment failure result in an alteration of host cell entry factor use and escape from neutralizing antibodies, suggesting that virus-host interactions during viral entry contribute to treatment failure.

Affiliations:

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Le document en format XML

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<wicri:noCountry>INC</wicri:noCountry>
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<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Université de Strasbourg</s1>
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<publicationStmt><idno type="wicri:source">INIST</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Hepatitis C Virus Envelope Glycoprotein Signatures Are Associated With Treatment Failure and Modulation of Viral Entry and Neutralization</title>
<author><name sortKey="Schvoerer, Evelyne" sort="Schvoerer, Evelyne" uniqKey="Schvoerer E" first="Evelyne" last="Schvoerer">Evelyne Schvoerer</name>
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</inist:fA14>
<wicri:noCountry>INC</wicri:noCountry>
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<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Université de Strasbourg</s1>
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<wicri:noCountry>INC</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Moenne Loccoz, Remy" sort="Moenne Loccoz, Remy" uniqKey="Moenne Loccoz R" first="Rémy" last="Moenne-Loccoz">Rémy Moenne-Loccoz</name>
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<wicri:noCountry>INC</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Université de Strasbourg</s1>
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<author><name sortKey="Murray, John M" sort="Murray, John M" uniqKey="Murray J" first="John M." last="Murray">John M. Murray</name>
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<affiliation wicri:level="3"><inist:fA14 i1="06"><s1>The Kirby Institute, University of New South Wales</s1>
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<country>Australie</country>
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<author><name sortKey="Velar, Aurelie" sort="Velar, Aurelie" uniqKey="Velar A" first="Aurélie" last="Velar">Aurélie Velar</name>
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<wicri:noCountry>INC</wicri:noCountry>
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<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Université de Strasbourg</s1>
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<wicri:noCountry>INC</wicri:noCountry>
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<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Université de Strasbourg</s1>
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<author><name sortKey="Fofana, Isabel" sort="Fofana, Isabel" uniqKey="Fofana I" first="Isabel" last="Fofana">Isabel Fofana</name>
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<wicri:noCountry>INC</wicri:noCountry>
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<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Université de Strasbourg</s1>
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<country>France</country>
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<author><name sortKey="Fafi Kremer, Samira" sort="Fafi Kremer, Samira" uniqKey="Fafi Kremer S" first="Samira" last="Fafi-Kremer">Samira Fafi-Kremer</name>
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<wicri:noCountry>INC</wicri:noCountry>
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<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Université de Strasbourg</s1>
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<country>France</country>
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<orgName type="university">Université de Strasbourg</orgName>
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<wicri:noCountry>INC</wicri:noCountry>
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<author><name sortKey="Erba, Anne Claire" sort="Erba, Anne Claire" uniqKey="Erba A" first="Anne-Claire" last="Erba">Anne-Claire Erba</name>
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<wicri:noCountry>INC</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Université de Strasbourg</s1>
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<author><name sortKey="Habersetzer, Francois" sort="Habersetzer, Francois" uniqKey="Habersetzer F" first="François" last="Habersetzer">François Habersetzer</name>
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<author><name sortKey="Baumert, Thomas F" sort="Baumert, Thomas F" uniqKey="Baumert T" first="Thomas F." last="Baumert">Thomas F. Baumert</name>
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</analytic>
<series><title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
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</sourceDesc>
<seriesStmt><title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Failure</term>
<term>Glycoprotein</term>
<term>Hepatitis C virus</term>
<term>Infection</term>
<term>Neutralization</term>
<term>Treatment</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Virus hépatite C</term>
<term>Glycoprotéine</term>
<term>Traitement</term>
<term>Echec</term>
<term>Neutralisation</term>
<term>Infection</term>
</keywords>
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<front><div type="abstract" xml:lang="en">Background. A major challenge for antiviral treatment of hepatitis C virus (HCV) infection is viral resistance, potentially resulting from the high variability of HCV envelope glycoproteins and subsequent selection of strains with enhanced infectivity and/or immune escape. Methods. We used a bioinformatics and functional approach to investigate whether E1/E2 envelope glycoprotein structure and function were associated with treatment failure in 92 patients infected with HCV genotype 1. Results. Bioinformatics analysis identified 1 sustain virological response (R)-related residue in E1 (219T) and 2 non-SVR (NR)-related molecular signatures in E2 (431A and 642V) in HCV genotype 1a. Two of these positions also appeared in minimal networks separating NR patients from R patients. HCV pseudoparticles (HCVpp) expressing 431A and 642V resulted in a decrease in antibody-mediated neutralization by pretreatment sera. 431A/ HCVpp entry into Huh7.5 cells increased with overexpression of CD81 and SR-BI. Moreover, an association of envelope glycoprotein signatures with treatment failure was confirmed in an independent cohort (Virahep-C). Conclusions. Combined in silico and functional analyses demonstrate that envelope glycoprotein signatures associated with treatment failure result in an alteration of host cell entry factor use and escape from neutralizing antibodies, suggesting that virus-host interactions during viral entry contribute to treatment failure.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>France</li>
<li>États-Unis</li>
</country>
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<li>Grand Est</li>
<li>Missouri (État)</li>
<li>Nouvelle-Galles du Sud</li>
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<name sortKey="Doffoel, Michel" sort="Doffoel, Michel" uniqKey="Doffoel M" first="Michel" last="Doffoël">Michel Doffoël</name>
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<name sortKey="Fafi Kremer, Samira" sort="Fafi Kremer, Samira" uniqKey="Fafi Kremer S" first="Samira" last="Fafi-Kremer">Samira Fafi-Kremer</name>
<name sortKey="Fofana, Isabel" sort="Fofana, Isabel" uniqKey="Fofana I" first="Isabel" last="Fofana">Isabel Fofana</name>
<name sortKey="Gut, Jean Pierre" sort="Gut, Jean Pierre" uniqKey="Gut J" first="Jean-Pierre" last="Gut">Jean-Pierre Gut</name>
<name sortKey="Habersetzer, Francois" sort="Habersetzer, Francois" uniqKey="Habersetzer F" first="François" last="Habersetzer">François Habersetzer</name>
<name sortKey="Habersetzer, Francois" sort="Habersetzer, Francois" uniqKey="Habersetzer F" first="François" last="Habersetzer">François Habersetzer</name>
<name sortKey="Moenne Loccoz, Remy" sort="Moenne Loccoz, Remy" uniqKey="Moenne Loccoz R" first="Rémy" last="Moenne-Loccoz">Rémy Moenne-Loccoz</name>
<name sortKey="Stoll Keller, Francoise" sort="Stoll Keller, Francoise" uniqKey="Stoll Keller F" first="Françoise" last="Stoll-Keller">Françoise Stoll-Keller</name>
<name sortKey="Turek, Marine" sort="Turek, Marine" uniqKey="Turek M" first="Marine" last="Turek">Marine Turek</name>
<name sortKey="Velar, Aurelie" sort="Velar, Aurelie" uniqKey="Velar A" first="Aurélie" last="Velar">Aurélie Velar</name>
<name sortKey="Zeisel, Mirjam B" sort="Zeisel, Mirjam B" uniqKey="Zeisel M" first="Mirjam B." last="Zeisel">Mirjam B. Zeisel</name>
</country>
<country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Murray, John M" sort="Murray, John M" uniqKey="Murray J" first="John M." last="Murray">John M. Murray</name>
</region>
</country>
<country name="États-Unis"><noRegion><name sortKey="Donlin, Maureen J" sort="Donlin, Maureen J" uniqKey="Donlin M" first="Maureen J." last="Donlin">Maureen J. Donlin</name>
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<name sortKey="Donlin, Maureen J" sort="Donlin, Maureen J" uniqKey="Donlin M" first="Maureen J." last="Donlin">Maureen J. Donlin</name>
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<name sortKey="Tavis, John E" sort="Tavis, John E" uniqKey="Tavis J" first="John E." last="Tavis">John E. Tavis</name>
</country>
</tree>
</affiliations>
</record>

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Hepatitis C Virus Envelope Glycoprotein Signatures Are Associated With Treatment Failure and Modulation of Viral Entry and Neutralization

Hepatitis C Virus Envelope Glycoprotein Signatures Are Associated With Treatment Failure and Modulation of Viral Entry and Neutralization

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