Universität zu Köln

Edwards, Suzanne, Stucki, Heinz, Bader, Joelle, Vidal, Vincent, Kaiser, Rolf, Battegay, Manuel and Klimkait, Thomas ORCID: 0000-0003-4945-6511 (2015). A Diagnostic HIV-1 Tropism System Based on Sequence Relatedness. J. Clin. Microbiol., 53 (2). S. 597 - 611. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-660X

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Edwards, Suzanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Stucki, Heinz UNSPECIFIED UNSPECIFIED UNSPECIFIED Bader, Joelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Vidal, Vincent UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaiser, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Battegay, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Klimkait, Thomas UNSPECIFIED orcid.org/0000-0003-4945-6511 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-413501
DOI:	10.1128/JCM.02762-14
Journal or Publication Title:	J. Clin. Microbiol.
Volume:	53
Number:	2
Page Range:	S. 597 - 611
Date:	2015
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-660X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IMMUNODEFICIENCY-VIRUS TYPE-1; HETERODUPLEX TRACKING ASSAY; CORECEPTOR TROPISM; CCR5 ANTAGONIST; SMALL-MOLECULE; CXCR4 TROPISM; ENHANCED SENSITIVITY; CHEMOKINE RECEPTOR; HIGH PREVALENCE; VIRAL TROPISM Multiple languages Microbiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41350