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Thirty-one SI HIV-1 isolates were studied (12 from the acute and 19 from the chronic stage). Infection capacity dependent on CXCR4 only (X4) or on both CXCR4 and CCR5 (R5X4) was determined by re-infection on two cell systems: PHA-activated PBMCs and GHOST coreceptor-ransfected cells using CXCR4 blockers when necessary. Coreceptor usage strikingly differed between those two cell systems. On GHOST cells 95% of SI-isolates were dual tropic (R5X4). On PBMCs, strains obtained at acute infection were predominantly R5X4 (75%), while 70% of SI HIV-1 from chronic stages was X4. In addition, four V3-loop-sequence-based algorithms were applied to the previously mentioned isolates in order to classify them as R5 or X4/R5X4 variants (the net charge, 11/25 rule, PSSM and geno2pheno). Only 66% of SI isolates were classified as X4 using the bioinformatic algorithms. Our study demonstrated that computational algorithms were notoriously inaccurate in predicting tropism of SI-isolates, particularly for those obtained at primary infection since half of them were misclassified as R5 variants by three of the V3-sequence-based phenotype-predictor algorithms. In conclusion, SI variants coreceptor usage may vary according to the method used. Tropism determination of SI strains on PBMCs may more closely indicate the viral behavior in vivo since we use the natural virus target. Differences along the course of infection, such as predominance of dual-R5X4 tropic in the acute stage and prevalence of X4 variants in chronic infection, probably reflect the evolution of coreceptor usage of SI variants during pediatric infection. We also provide strong evidence suggesting that coreceptor usage of HIV-1 should be carefully determined before CCR5 blockers were implemented, particularly in pediatric infection. HIV-1 Coreceptors Children © 2015 Crudeli CM et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 2017-03-01T15:07:03+05:30 2017-03-01T15:07:05+05:30 2017-03-01T15:07:05+05:30 4 Adobe InDesign CS6 (Windows) uuid:f4c3c770-a927-4f07-9a5c-1ec771355ddc xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:3390C7A062FEE611B266C11E1C0250D8 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2017-03-01T15:07:03+05:30 xmp.iid:3BE43D4A62FEE611B266C11E1C0250D8 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Citation: Crudeli CM, Corró G, Rocco CA, Beltramone N, Marino SA, et al. (2015) Coreceptor Usage of Syncytium-Inducing- HIV-1 Isolates Depends on the Target Cell and Evolves during Pediatric Infection. J HIV AIDS Volume1.1: http://dx.doi.org/10.16966/2380-5536.102 Guillermo Corró, Hospital Distrital Lago Argentino “Dr. José Formenti” Avda. Julio A Roca 1487 (9405) El Calafate, Santa Cruz, Argentina, Tel: +54 2966 729443; E-mail: gcorro2@gmail.com, gcorro2@yahoo.com.ar Adobe PDF Library 10.0.1 False endstream endobj 456 0 obj <> endobj xref 0 3948 0000000000 65535 f 0000295262 00000 n 0000295717 00000 n 0000295776 00000 n 0000306169 00000 n 0000306228 00000 n 0000306685 00000 n 0000306708 00000 n 0000306841 00000 n 0000316330 00000 n 0000316414 00000 n 0000316474 00000 n 0000316973 00000 n 0000316998 00000 n 0000317133 00000 n 0000327318 00000 n 0000327403 00000 n 0000327463 00000 n 0000327976 00000 n 0000328001 00000 n 0000328136 00000 n 0000338870 00000 n 0000338955 00000 n 0000339015 00000 n 0000339544 00000 n 0000339569 00000 n 0000339704 00000 n 0000350510 00000 n 0000350622 00000 n 0000363783 00000 n 0000364056 00000 n 0000364373 00000 n 0000364458 00000 n 0000364518 00000 n 0000365053 00000 n 0000365750 00000 n 0000365885 00000 n 0000375617 00000 n 0000375702 00000 n 0000375762 00000 n 0000376195 00000 n 0000376652 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65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f trailer <<8AA770230807CA40A36ABB02D96E0151>]>> startxref 116 %%EOF 455 0 obj <>stream application/pdf Coreceptor Usage of Syncytium-Inducing-HIV-1 Isolates Depends on the Target Cell and Evolves during Pediatric Infection Cintia M Crudeli Guillermo Corró Carlos A Rocco Natalia Beltramone Silvia A Marino and Luisa Sen Comparisons between different phenotypic and sequence-based bioniformatic methods for coreceptor usage prediction were performed to establish the role and variation of syncytium-inducing (SI) HIV-1 phenotype on CCR5 and CXCR4 coreceptor usage along the course of vertical infection. Thirty-one SI HIV-1 isolates were studied (12 from the acute and 19 from the chronic stage). Infection capacity dependent on CXCR4 only (X4) or on both CXCR4 and CCR5 (R5X4) was determined by re-infection on two cell systems: PHA-activated PBMCs and GHOST coreceptor-ransfected cells using CXCR4 blockers when necessary. Coreceptor usage strikingly differed between those two cell systems. On GHOST cells 95% of SI-isolates were dual tropic (R5X4). On PBMCs, strains obtained at acute infection were predominantly R5X4 (75%), while 70% of SI HIV-1 from chronic stages was X4. In addition, four V3-loop-sequence-based algorithms were applied to the previously mentioned isolates in order to classify them as R5 or X4/R5X4 variants (the net charge, 11/25 rule, PSSM and geno2pheno). Only 66% of SI isolates were classified as X4 using the bioinformatic algorithms. Our study demonstrated that computational algorithms were notoriously inaccurate in predicting tropism of SI-isolates, particularly for those obtained at primary infection since half of them were misclassified as R5 variants by three of the V3-sequence-based phenotype-predictor algorithms. In conclusion, SI variants coreceptor usage may vary according to the method used. Tropism determination of SI strains on PBMCs may more closely indicate the viral behavior in vivo since we use the natural virus target. Differences along the course of infection, such as predominance of dual-R5X4 tropic in the acute stage and prevalence of X4 variants in chronic infection, probably reflect the evolution of coreceptor usage of SI variants during pediatric infection. We also provide strong evidence suggesting that coreceptor usage of HIV-1 should be carefully determined before CCR5 blockers were implemented, particularly in pediatric infection. HIV-1 Coreceptors Children © 2015 Crudeli CM et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 2017-03-01T15:07:03+05:30 2017-03-01T15:07:09+05:30 2017-03-01T15:07:09+05:30 4 Adobe InDesign CS6 (Windows) uuid:c356f62b-d3ec-4aa4-8143-035366a68159 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:3390C7A062FEE611B266C11E1C0250D8 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2017-03-01T15:07:03+05:30 xmp.iid:3BE43D4A62FEE611B266C11E1C0250D8 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Citation: Crudeli CM, Corró G, Rocco CA, Beltramone N, Marino SA, et al. (2015) Coreceptor Usage of Syncytium-Inducing- HIV-1 Isolates Depends on the Target Cell and Evolves during Pediatric Infection. J HIV AIDS Volume1.1: http://dx.doi.org/10.16966/2380-5536.102 Guillermo Corró, Hospital Distrital Lago Argentino “Dr. José Formenti” Avda. Julio A Roca 1487 (9405) El Calafate, Santa Cruz, Argentina, Tel: +54 2966 729443; E-mail: gcorro2@gmail.com, gcorro2@yahoo.com.ar Adobe PDF Library 10.0.1 False endstream endobj 456 0 obj <> endobj 3949 0 obj <>/Metadata 455 0 R/Names 3950 0 R/Outlines 369 0 R/PageMode/UseOutlines/Pages 454 0 R/StructTreeRoot 457 0 R/Type/Catalog/ViewerPreferences<>>> endobj xref 0 1 0000000000 65535 f 455 2 0000674021 00000 n 0000682782 00000 n 3949 1 0000685246 00000 n trailer <]/Prev 116>> startxref 685450 %%EOF