Marty, Nina, Saeng-Aroon, Siriphan, Heger, Eva, Thielen, Alexander, Obermeier, Martin, Pfeifer, Nico, Kaiser, Rolf and Klimkait, Thomas ORCID: 0000-0003-4945-6511 (2021). Adapting the geno2pheno[coreceptor] tool to HIV-1 subtype CRF01_AE by phenotypic validation using clinical isolates from South-East Asia. J. Clin. Virol., 136. AMSTERDAM: ELSEVIER. ISSN 1873-5967

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Abstract

Objectives: Geno2pheno[coreceptor] is a widely used tool for the prediction of coreceptor usage (viral tropism) of HIV-1 samples. For HIV-1 CRF01_AE, a significant overcalling of X4-tropism is observed when using the standard settings of Geno2pheno[coreceptor]. The aim of this study was to provide the experimental backing for adaptations to the geno2pheno[coreceptor] algorithm in order to improve coreceptor usage predictions of clinical HIV-1 CRF01_AE isolates Study design: V3-sequences of 20 clinical HIV-1 subtype CRF01_AE samples were sequenced and analyzed by geno2pheno[coreceptor]. In parallel, coreceptor usage was determined for these samples by replicative phenotyping in human cells in the presence of specific X4-or R5-inhibitors. Results: The sole introduction of the CRF01_AE V3 region into a full-length otherwise subtype B provirus failed to produce replication-competent viral progeny. A successive genome-replacement strategy revealed that also CRF01_AE derived gag and pol sequences are necessary to generate HIV genomes with sufficient replication competence. Subsequent phenotypic analysis confirmed overcalling of X4-tropism for CRF01_AE viruses using the current version and the standard cut-off at 10% false positive rate (FPR) of geno2pheno[coreceptor]. Lowering the FPR cut-off to 2.5% reduced the X4-overcalling in our sample collection, while still allowing a safe administration of Maraviroc (MCV). Conclusion: This study demonstrates the successful adjustment of geno2pheno[coreceptor] rules for subtype CRF01_AE. It also supports the unique strength of combining complementing methods, namely phenotyping and genotyping, for validating new bioinformatics tools prior to application in diagnostics.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Marty, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saeng-Aroon, SiriphanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heger, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thielen, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Obermeier, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfeifer, NicoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiser, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klimkait, ThomasUNSPECIFIEDorcid.org/0000-0003-4945-6511UNSPECIFIED
URN: urn:nbn:de:hbz:38-591578
DOI: 10.1016/j.jcv.2021.104755
Journal or Publication Title: J. Clin. Virol.
Volume: 136
Date: 2021
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1873-5967
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
VirologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59157

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