Evaluation of genotypic tropism prediction tests compared with in vitro co-receptor usage in HIV-1 primary isolates of diverse subtypes

Delgado, Elena; Fernández-García, Aurora; Vega, Yolanda; Cuevas, Teresa; Pinilla, Milagros; Garcia, Valentina E.; Sánchez, Mónica; González, María del Mar; Sánchez, Ana M.; Thomson, Michael M.; Pérez-Álvarez, Lucı́a

doi:10.1093/jac/dkr438

Cited by 40 publications

(39 citation statements)

References 44 publications

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“…Geno2pheno with a 10% cutoff has been recommended for V3 genotyping (22). Recent evaluations of genotypic algorithms for predicting tropism of non-B subtype viruses showed good agreement with the phenotype, but the CRF01-AE subtype was not included (6,23). Moreover, we have shown that these genotypic tools are not valid for predicting the tropism of subtype D viruses (8).…”

Section: Discussionmentioning

confidence: 99%

“…Genetic variations in the envelope gene influence the genotypic prediction of HIV-1 tropism that relies on data on the correlation between genotype and phenotype obtained in countries where subtype B viruses predominate. But the performance of genotypic algorithms can differ from one HIV-1 subtype to another and must be validated for each particular subtype (6)(7)(8)(9)(10)(11).…”

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confidence: 99%

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Genotypic Prediction of HIV-1 CRF01-AE Tropism

et al. 2013

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f HIV-1 subtype CRF01-AE predominates in south Asia and has spread throughout the world. The virus tropism must be determined before using CCR5 antagonists. Genotypic methods could be used, but the prediction algorithms may be inaccurate for non-B subtypes like CRF01-AE and the correlation with the phenotypic approach has not been assessed. We analyzed 61 CRF01-AE V3 clonal sequences of known phenotype from the GenBank database. The sensitivity of the Geno2pheno10 genotypic algorithm was 91%, but its specificity was poor (54%). In contrast, the combined 11/25 and net charge rule was highly specific (98%) but rather insensitive (64%). We thus identified subtype CRF01-AE determinants in the V3 region that are associated with CXCR4 use and developed a new simple rule for optimizing the genotypic prediction of CRF01-AE tropism. The concordance between the predicted CRF01-AE genotype and the phenotype was 95% for the clonal data set. We then validated this algorithm by analyzing the data from 44 patients infected with subtype CRF01-AE, whose tropism was determined using a recombinant phenotypic entry assay and V3-loop bulk sequencing. The CRF01-AE genotypic tool was 70% sensitive and 96% specific for predicting CXCR4 use, and the concordance between genotype and phenotype was 84%, approaching the concordance obtained for predicting the tropism of HIV-1 subtype B. Genotypic predictions that use a subtype CRF01-AE-specific algorithm appear to be preferable for characterizing coreceptor usage both in pathophysiological studies and for ensuring the appropriate use of CCR5 antagonists.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Genotypic Prediction of HIV-1 CRF01-AE Tropism

et al. 2013

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“…Los análisis filogenéticos de secuencias pertenecientes al cluster de subsubtipo F1 que se ha expandido recientemente en Galicia, Thomson et al (2012) varios países europeos estrechamente relacionados con el cluster F de Galicia, que ramifican en posición basal al mismo y la mayoría recolectados varios años antes de la expansión del cluster gallego, Thomson et al (2012) indica que dicho cluster procede de una variante que se expandió previamente por varios países de Europa occidental. Por otra parte, el hecho de que los 7 virus relacionados con el cluster F de Galicia de los que hay datos epidemiológicos todos proceden de varones infectados por vía sexual y 6 son HSH (los dos de Valladolid, dos de Suiza y los dos de Bélgica) sugiere que la variante europea a partir de la cual se originó el cluster de Galicia también se transmite por contacto homosexual.…”

Section: Discussionunclassified

Análisis de secuencias de la envoltura y de genomas completos de virus de un cluster de VIH-1 de subtipo f de rápida expansión en Galicia: predicción de uso de correceptores y filogenia

Palao

Vega

Delgado

et al. 2012

Revista Complutense De Ciencias Veterinarias

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Carlos III Majadahonda, Madrid. Correspondencia con el autor: lperezal@isciii.es RESUMENLa epidemia por VIH-1 en España, al igual que en el resto de Europa occidental, está dominada por el subtipo B. Sin embargo, recientemente se ha descrito la rápida expansión de un cluster de subsubtipo F1 entre hombres que tienen relaciones sexuales con hombres en Galicia. Los objetivos de este trabajo son analizar la secuencia de la envoltura de los virus del mencionado cluster para predicción de utilización de correceptores y presencia de aminoácidos característicos, así como caracterizar secuencias de genomas completos, determinando las relaciones filogenéticas con virus de subtipo F de otros países. Los análisis filogenéticos permitieron determinar relaciones del cluster F con virus de Brasil, Suiza, Bélgica, Francia y Gran Bretaña. Por otra parte, se han encontrado posiciones características del cluster en la región V3, diferentes de otras cepas F1, así como en otras regiones de la envoltura. Aparte, se han identificado mutaciones características asociadas a tropismo X4. El cluster de VIH-1 de subtipo F recientemente expandido en Galicia procede de una variante ampliamente diseminada en Europa occidental. Los virus de dicho cluster presentan aminoácidos característicos en la envoltura, identificándose en algunos de ellos mutaciones asociadas a tropismo X4, de potencial relevancia biológica.

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“…8,9 Of the variable domains, the V3 loop has the strongest known link with HIV-1 tropism, and, therefore, V3 is frequently the focus of studies that aim at defining tropism states. Computational approaches have been developed to classify viruses as R5 or X4 tropic based on a small number of genotypic features of the envelope V3 domain, including charge, number of glycosylation motifs and domain length, [10][11][12][13][14] or the ''11/25 rule'' that associates positively charged amino acids at two positions (11 and 25) in the V3 loop. 15 These methods are highly useful in classifying HIV-1 subtypes B and C as either R5 or X4 tropic so that the appropriate therapy can be prescribed.…”

Section: H Uman Immunodeficiency Virus Type 1 (Hiv-1) Primarily Infecmentioning

confidence: 99%

On the Physicochemical and Structural Modifications Associated with HIV-1 Subtype B Tropism Transition

LamersSusanna¹,

FogelGary

LiuEnoch

et al. 2016

AIDS Research and Human Retroviruses

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HIV-1 enters immune cells via binding the viral envelope to a host cell CD4 receptor, and then a secondary coreceptor, usually CCR5 (R5) or CXCR4 (X4), and some HIV can utilize both co-receptors (R5X4). Although a small set of amino-acid properties such as charge and sequence length applied to HIV-1 envelope V3 loop sequence data can be used to predict co-receptor usage, we sought to expand the fundamental understanding of the physiochemical basis of tropism by analyzing many, perhaps less obvious, amino-acid properties over a diverse array of HIV sequences. We examined 74 amino-acid physicochemical scales over 1,559 V3 loop sequences with biologically tested tropisms downloaded from the Los Alamos HIV sequence database. Linear regressions were then calculated for each feature relative to three tropism transitions (R5/X4; R5/R5X4; R5X4/X4). Independent correlations were rank ordered to determine informative features. A structural analysis of the V3 loop was performed to better interpret these findings relative to HIV tropism states. Similar structural changes are required for R5 and R5X4 to transition to X4, thus suggesting that R5 and R5X4 types are more similar than either phenotype is to X4. Overall, the analysis suggests a continuum of viral tropism that is only partially related to charge; in fact, the analysis suggests that charge modification may be primarily attributed to decreased R5 usage, and further structural changes, particularly those associated with b-sheet structure, are likely required for full X4 usage.

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Evaluation of genotypic tropism prediction tests compared with in vitro co-receptor usage in HIV-1 primary isolates of diverse subtypes

Cited by 40 publications

References 44 publications

Genotypic Prediction of HIV-1 CRF01-AE Tropism

Genotypic Prediction of HIV-1 CRF01-AE Tropism

Análisis de secuencias de la envoltura y de genomas completos de virus de un cluster de VIH-1 de subtipo f de rápida expansión en Galicia: predicción de uso de correceptores y filogenia

On the Physicochemical and Structural Modifications Associated with HIV-1 Subtype B Tropism Transition

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