HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].

<h4>Background</h4>Human Immunodeficiency virus type-1 (HIV) entry into target cells involves binding of the viral envelope (Env) to CD4 and a coreceptor, mainly CCR5 or CXCR4. The only currently licensed HIV entry inhibitor, maraviroc, targets CCR5, and the presence of CXCX4-using strai...

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Autores principales:	Martin Mulinge, Morgane Lemaire, Jean-Yves Servais, Arkadiusz Rybicki, Daniel Struck, Eveline Santos da Silva, Chris Verhofstede, Yolanda Lie, Carole Seguin-Devaux, Jean-Claude Schmit, Danielle Perez Bercoff
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fa11ab77848e4cfbb4d04d1cf5e57b17
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spelling	oai:doaj.org-article:fa11ab77848e4cfbb4d04d1cf5e57b172021-11-18T07:46:24ZHIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].1932-620310.1371/journal.pone.0060566https://doaj.org/article/fa11ab77848e4cfbb4d04d1cf5e57b172013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23667426/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Human Immunodeficiency virus type-1 (HIV) entry into target cells involves binding of the viral envelope (Env) to CD4 and a coreceptor, mainly CCR5 or CXCR4. The only currently licensed HIV entry inhibitor, maraviroc, targets CCR5, and the presence of CXCX4-using strains must be excluded prior to treatment. Co-receptor usage can be assessed by phenotypic assays or through genotypic prediction. Here we compared the performance of a phenotypic Env-Recombinant Viral Assay (RVA) to the two most widely used genotypic prediction algorithms, Geno2Pheno[coreceptor] and webPSSM.<h4>Methods</h4>Co-receptor tropism of samples from 73 subtype B and 219 non-B infections was measured phenotypically using a luciferase-tagged, NL4-3-based, RVA targeting Env. In parallel, tropism was inferred genotypically from the corresponding V3-loop sequences using Geno2Pheno[coreceptor] (5-20% FPR) and webPSSM-R5X4. For discordant samples, phenotypic outcome was retested using co-receptor antagonists or the validated Trofile® Enhanced-Sensitivity-Tropism-Assay.<h4>Results</h4>The lower detection limit of the RVA was 2.5% and 5% for X4 and R5 minority variants respectively. A phenotype/genotype result was obtained for 210 samples. Overall, concordance of phenotypic results with Geno2Pheno[coreceptor] was 85.2% and concordance with webPSSM was 79.5%. For subtype B, concordance with Geno2pheno[coreceptor] was 94.4% and concordance with webPSSM was 79.6%. High concordance of genotypic tools with phenotypic outcome was seen for subtype C (90% for both tools). Main discordances involved CRF01_AE and CRF02_AG for both algorithms (CRF01_AE: 35.9% discordances with Geno2Pheno[coreceptor] and 28.2% with webPSSM; CRF02_AG: 20.7% for both algorithms). Genotypic prediction overestimated CXCR4-usage for both CRFs. For webPSSM, 40% discordance was observed for subtype A.<h4>Conclusions</h4>Phenotypic assays remain the most accurate for most non-B subtypes and new subtype-specific rules should be developed for non-B subtypes, as research studies more and more draw conclusions from genotypically-inferred tropism, and to avoid unnecessarily precluding patients with limited treatment options from receiving maraviroc or other entry inhibitors.Martin MulingeMorgane LemaireJean-Yves ServaisArkadiusz RybickiDaniel StruckEveline Santos da SilvaChris VerhofstedeYolanda LieCarole Seguin-DevauxJean-Claude SchmitDanielle Perez BercoffPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e60566 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martin Mulinge Morgane Lemaire Jean-Yves Servais Arkadiusz Rybicki Daniel Struck Eveline Santos da Silva Chris Verhofstede Yolanda Lie Carole Seguin-Devaux Jean-Claude Schmit Danielle Perez Bercoff HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].
description	<h4>Background</h4>Human Immunodeficiency virus type-1 (HIV) entry into target cells involves binding of the viral envelope (Env) to CD4 and a coreceptor, mainly CCR5 or CXCR4. The only currently licensed HIV entry inhibitor, maraviroc, targets CCR5, and the presence of CXCX4-using strains must be excluded prior to treatment. Co-receptor usage can be assessed by phenotypic assays or through genotypic prediction. Here we compared the performance of a phenotypic Env-Recombinant Viral Assay (RVA) to the two most widely used genotypic prediction algorithms, Geno2Pheno[coreceptor] and webPSSM.<h4>Methods</h4>Co-receptor tropism of samples from 73 subtype B and 219 non-B infections was measured phenotypically using a luciferase-tagged, NL4-3-based, RVA targeting Env. In parallel, tropism was inferred genotypically from the corresponding V3-loop sequences using Geno2Pheno[coreceptor] (5-20% FPR) and webPSSM-R5X4. For discordant samples, phenotypic outcome was retested using co-receptor antagonists or the validated Trofile® Enhanced-Sensitivity-Tropism-Assay.<h4>Results</h4>The lower detection limit of the RVA was 2.5% and 5% for X4 and R5 minority variants respectively. A phenotype/genotype result was obtained for 210 samples. Overall, concordance of phenotypic results with Geno2Pheno[coreceptor] was 85.2% and concordance with webPSSM was 79.5%. For subtype B, concordance with Geno2pheno[coreceptor] was 94.4% and concordance with webPSSM was 79.6%. High concordance of genotypic tools with phenotypic outcome was seen for subtype C (90% for both tools). Main discordances involved CRF01_AE and CRF02_AG for both algorithms (CRF01_AE: 35.9% discordances with Geno2Pheno[coreceptor] and 28.2% with webPSSM; CRF02_AG: 20.7% for both algorithms). Genotypic prediction overestimated CXCR4-usage for both CRFs. For webPSSM, 40% discordance was observed for subtype A.<h4>Conclusions</h4>Phenotypic assays remain the most accurate for most non-B subtypes and new subtype-specific rules should be developed for non-B subtypes, as research studies more and more draw conclusions from genotypically-inferred tropism, and to avoid unnecessarily precluding patients with limited treatment options from receiving maraviroc or other entry inhibitors.
format	article
author	Martin Mulinge Morgane Lemaire Jean-Yves Servais Arkadiusz Rybicki Daniel Struck Eveline Santos da Silva Chris Verhofstede Yolanda Lie Carole Seguin-Devaux Jean-Claude Schmit Danielle Perez Bercoff
author_facet	Martin Mulinge Morgane Lemaire Jean-Yves Servais Arkadiusz Rybicki Daniel Struck Eveline Santos da Silva Chris Verhofstede Yolanda Lie Carole Seguin-Devaux Jean-Claude Schmit Danielle Perez Bercoff
author_sort	Martin Mulinge
title	HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].
title_short	HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].
title_full	HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].
title_fullStr	HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].
title_full_unstemmed	HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].
title_sort	hiv-1 tropism determination using a phenotypic env recombinant viral assay highlights overestimation of cxcr4-usage by genotypic prediction algorithms for crf01_ae and crf02_ag [corrected].
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/fa11ab77848e4cfbb4d04d1cf5e57b17
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HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected].

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