A diagnostic HIV-1 tropism system based on sequence relatedness

Edwards, Suzanne and Stucki, Heinz and Bader, Joëlle and Vidal, Vincent and Kaiser, Rolf and Battegay, Manuel and Klimkait, Thomas and Swiss, H. I. V. Cohort Study. (2015) A diagnostic HIV-1 tropism system based on sequence relatedness. Journal of Clinical Microbiology, 53 (2). pp. 597-610.

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Official URL: https://edoc.unibas.ch/62192/

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Key clinical studies for HIV coreceptor antagonists have used the phenotyping-based Trofile test. Meanwhile various simpler-to-do genotypic tests have become available that are compatible with standard laboratory equipment and Web-based interpretation tools. However, these systems typically analyze only the most prominent virus sequence in a specimen. We present a new diagnostic HIV tropism test not needing DNA sequencing. The system, XTrack, uses physical properties of DNA duplexes after hybridization of single-stranded HIV-1 env V3 loop probes to the clinical specimen. Resulting "heteroduplexes" possess unique properties driven by sequence relatedness to the reference and resulting in a discrete electrophoretic mobility. A detailed optimization process identified diagnostic probe candidates relating best to a large number of HIV-1 sequences with known tropism. From over 500 V3 sequences representing all main HIV-1 subtypes (Los Alamos database), we obtained a small set of probes to determine the tropism in clinical samples. We found a high concordance with the commercial TrofileES test (84.9%) and the Web-based tool Geno2Pheno (83.0%). Moreover, the new system reveals mixed virus populations, and it was successful on specimens with low virus loads or on provirus from leukocytes. A replicative phenotyping system was used for validation. Our data show that the XTrack test is favorably suitable for routine diagnostics. It detects and dissects mixed virus populations and viral minorities; samples with viral loads (VL) of >200 copies/ml are successfully analyzed. We further expect that the principles of the platform can be adapted also to other sequence-divergent pathogens, such as hepatitis B and C viruses.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Molecular Virology (Klimkait)
UniBasel Contributors:Klimkait, Thomas
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1098-660X (Electronic) 0095-1137 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:17 Nov 2018 13:58
Deposited On:17 Nov 2018 13:58

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