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HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays

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dc.contributor.author Vandenbroucke, I.
dc.contributor.author Van Marck, H.
dc.contributor.author Mostmans, W.
dc.contributor.author Van Eygen, V.
dc.contributor.author Rondelez, E.
dc.contributor.author Thys, K.
dc.contributor.author Van Baelen, K.
dc.contributor.author Fransen, K.
dc.contributor.author Vaira, D.
dc.contributor.author Kabeya, K.
dc.contributor.author De Wit, S.
dc.contributor.author Florence, E.
dc.contributor.author Moutschen, M.
dc.contributor.author Vandekerckhove, L.
dc.contributor.author Verhofstede, C.
dc.contributor.author Stuyver, L.
dc.date.accessioned 2010-06-15T13:24:04Z
dc.date.available 2010-06-15T13:24:04Z
dc.date.issued 2010
dc.identifier.issn 1742-6405
dc.identifier.doi http://dx.doi.org/10.1186/1742-6405-7-4
dc.identifier.other ITG-M8A
dc.identifier.other ITG-C11A
dc.identifier.other MULTI
dc.identifier.other MICRO
dc.identifier.other CLINIC
dc.identifier.other U-HIVSTD
dc.identifier.other DOI
dc.identifier.other URL
dc.identifier.other FTA
dc.identifier.other UPD22
dc.identifier.other Electronic
dc.identifier.other Abstract
dc.identifier.uri http://hdl.handle.net/10390/6180
dc.description.abstract BACKGROUND:HIV-1 infected patients for whom standard gp160 phenotypic tropism testing failed are currently excluded from co-receptor antagonist treatment. To provide patients with maximal treatment options, massively parallel sequencing of the envelope V3 domain, in combination with tropism prediction tools, was evaluated as an alternative tropism determination strategy. Plasma samples from twelve HIV-1 infected individuals with failing phenotyping results were available. The samples were submitted to massive parallel sequencing and to confirmatory recombinant phenotyping using a fraction of the gp120 domain.RESULTS:A cut-off for sequence reads interpretation of 5 to10 times the sequencing error rate (0.2%) was implemented. On average, each sample contained 7 different V3 haplotypes. V3 haplotypes were submitted to tropism prediction algorithms, and 4/14 samples returned with presence of a dual/mixed (D/M) tropic virus, respectively at 3%, 10%, 11%, and 95% of the viral quasispecies. V3 tropism prediction was confirmed by gp120 phenotyping, except for two out of 4 D/M predicted viruses (with 3 and 95%) which were phenotypically R5-tropic. In the first case, the result was discordant due to the limit of detection for the phenotyping technology, while in the latter case the prediction algorithms were not computing the viral tropism correctly.CONCLUSIONS:Although only demonstrated on a limited set of samples, the potential of the combined use of "deep sequencing + prediction algorithms" in cases where routine gp160 phenotype testing cannot be employed was illustrated. While good concordance was observed between gp120 phenotyping and prediction of R5-tropic virus, the results suggest that accurate prediction of X4-tropic virus would require further algorithm development en
dc.language English en
dc.subject Viral diseases en
dc.subject HIV-1 en
dc.subject AIDS en
dc.subject Testing en
dc.subject Phenotyping en
dc.subject GP160 en
dc.subject GP120 en
dc.subject Envelope en
dc.subject Sequencing en
dc.subject Prediction en
dc.subject Algorithms en
dc.subject Tools en
dc.subject Evaluation en
dc.subject Haplotypes en
dc.title HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays en
dc.type Article-E en
dc.citation.issue 4 en
dc.citation.jtitle AIDS Research and Therapy en
dc.citation.volume 7 en
dc.citation.pages 1-6 en
dc.identifier.url http://www.aidsrestherapy.com/content/7/1/4
dc.citation.jabbreviation AIDS Res Ther en


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