Universität zu Köln

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

Full text not available from this repository.

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:	Creators Email ORCID ORCID Put Code Marty, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Saeng-Aroon, Siriphan UNSPECIFIED UNSPECIFIED UNSPECIFIED Heger, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Thielen, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Obermeier, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfeifer, Nico UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaiser, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Klimkait, Thomas UNSPECIFIED orcid.org/0000-0003-4945-6511 UNSPECIFIED
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:	Keywords Language Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59157