Počet záznamů: 1
Sensitive Cell-Based Assay for Determination of Human Immunodeficiency Virus Type 1 Coreceptor Tropism
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SYSNO ASEP 0393023 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Sensitive Cell-Based Assay for Determination of Human Immunodeficiency Virus Type 1 Coreceptor Tropism Tvůrce(i) Weber, Jan (UOCHB-X) RID, ORCID
Vazquez, A. C. (US)
Winner, D. (US)
Gibson, R. M. (US)
Rhea, A. M. (US)
Rose, J. D. (US)
Wylie, D. (US)
Henry, K. (US)
Wright, A. (US)
King, K. (US)
Archer, J. (GB)
Poveda, E. (ES)
Soriano, V. (ES)
Robertson, D. L. (GB)
Olivo, P. D. (US)
Arts, E. J. (US)
Quinones-Mateu, M. E. (US)Celkový počet autorů 17 Zdroj.dok. Journal of Clinical Microbiology - ISSN 0095-1137
Roč. 51, č. 5 (2013), s. 1517-1527Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova HIV tropism ; phenotypic assay ; genotypic prediction ; disease progression ; CCR5 antagonists ; naive patients Vědní obor RIV EE - Mikrobiologie, virologie Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000317602100027 EID SCOPUS 84876750679 DOI 10.1128/JCM.00092-13 Anotace CCR5 antagonists are a powerful new class of antiretroviral drugs that require a companion assay to evaluate the presence of CXCR4-tropic viruses prior to use in human immunodeficiency virus (HIV)-infected individuals. In this study, we have developed, characterized, verified, and prevalidated a novel phenotypic test to determine HIV-1 coreceptor tropism (VERITROP) based on a sensitive cell-to-cell fusion assay. The env-expressing vectors were used in a cell-to-cell fusion assay to determine the presence of R5 and/or non-R5 HIV-1 variants within the viral population. Results were compared with (i) the original version of Trofile, (ii) population sequencing, and (iii) 454 pyrosequencing, with the genotypic data analyzed using several bioinformatics tools, i. e., the 11/24/25 rule, Geno2Pheno, and webPSSM. VERITROP consistently detected minority non-R5 variants from clinical specimens, with an analytical sensitivity of 0.3%, with viral loads of >= 1,000 copies/ml, and from B and non-B subtypes. In a pilot study, a 73.7% (56/76) concordance was observed with the original Trofile assay, with 19 of the 20 discordant results corresponding to non-R5 variants detected using VERITROP and not by the original Trofile assay. The degree of concordance of VERITROP and Trofile with population and deep sequencing results depended on the algorithm used to determine HIV-1 coreceptor tropism. Overall, VERITROP showed better concordance with deep sequencing/Geno2Pheno at a 0.3% detection threshold (67%), whereas Trofile matched better with population sequencing (79%). However, 454 sequencing using Geno2Pheno at a 10% FPR and 0.3% threshold and VERITROP more accurately predicted the success of a maraviroc-based regimen. In conclusion, VERITROP may promote the development of new HIV coreceptor antagonists and aid in the treatment and management of HIV-infected individuals prior to and/or during treatment with this class of drugs. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Rok sběru 2014
Počet záznamů: 1