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Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate

HIV human immunodeficiency virus type I (HIV-1) entry inhibitor potency is dependent on viral co-receptor tropisms and thereby tropism determination is clinically important. However, phenotypic tropisms of HIV-1 non-B subtypes have been poorly investigated and the genotypic prediction algorithms rem...

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Autores principales: Judicate, George P., Barabona, Godfrey, Kamori, Doreen, Mahiti, Macdonald, Tan, Toong Seng, Ozono, Seiya, Mgunya, Amina Shaban, Kuwata, Takeo, Matsushita, Shuzo, Sunguya, Bruno, Lyamuya, Eligius, Tokunaga, Kenzo, Ueno, Takamasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292895/
https://www.ncbi.nlm.nih.gov/pubmed/34305873
http://dx.doi.org/10.3389/fmicb.2021.703041
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author Judicate, George P.
Barabona, Godfrey
Kamori, Doreen
Mahiti, Macdonald
Tan, Toong Seng
Ozono, Seiya
Mgunya, Amina Shaban
Kuwata, Takeo
Matsushita, Shuzo
Sunguya, Bruno
Lyamuya, Eligius
Tokunaga, Kenzo
Ueno, Takamasa
author_facet Judicate, George P.
Barabona, Godfrey
Kamori, Doreen
Mahiti, Macdonald
Tan, Toong Seng
Ozono, Seiya
Mgunya, Amina Shaban
Kuwata, Takeo
Matsushita, Shuzo
Sunguya, Bruno
Lyamuya, Eligius
Tokunaga, Kenzo
Ueno, Takamasa
author_sort Judicate, George P.
collection PubMed
description HIV human immunodeficiency virus type I (HIV-1) entry inhibitor potency is dependent on viral co-receptor tropisms and thereby tropism determination is clinically important. However, phenotypic tropisms of HIV-1 non-B subtypes have been poorly investigated and the genotypic prediction algorithms remain insufficiently validated. To clarify this issue, we recruited 52 treatment-naïve, HIV-1-infected patients in Tanzania, where multiple HIV-1 non-B subtypes co-circulate. Sequence analysis of 93 infectious envelope clones isolated from their plasma viral RNA revealed the co-circulation of subtypes A1, C, D, and inter-subtype recombinant forms (isRFs). Phenotypic tropism assays revealed that lentivirus reporters pseudotyped with 75 (80.6%) and 5 (5.4%) envelope clones could establish infection toward U87.CD4 cells expressing CCR5 (R5) and CXCR4 (X4), respectively; whereas the remaining 13 (14%) clones could infect both cells. Genotypic analyses by widely used algorithms including V3 net charge, Geno2pheno, WebPSSM, and PhenoSeq showed that almost all phenotypic X4-tropic clones and only 15 of 75 phenotypic R5-tropic clones were concordantly predicted. However, the remaining 60 phenotypic R5-tropic clones were discordantly predicted by at least one algorithm. In particular, 2 phenotypic R5-tropic clones were discordantly predicted by all algorithms tested. Taken together, the results demonstrate the limitation of currently available genotypic algorithms for predicting co-receptor inference among co-circulating multiple non-B subtypes and emerging isRFs. Also, the phenotypic tropism dataset presented here could be valuable for retraining of the widely used genotypic prediction algorithms to enhance their performance.
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spelling pubmed-82928952021-07-22 Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate Judicate, George P. Barabona, Godfrey Kamori, Doreen Mahiti, Macdonald Tan, Toong Seng Ozono, Seiya Mgunya, Amina Shaban Kuwata, Takeo Matsushita, Shuzo Sunguya, Bruno Lyamuya, Eligius Tokunaga, Kenzo Ueno, Takamasa Front Microbiol Microbiology HIV human immunodeficiency virus type I (HIV-1) entry inhibitor potency is dependent on viral co-receptor tropisms and thereby tropism determination is clinically important. However, phenotypic tropisms of HIV-1 non-B subtypes have been poorly investigated and the genotypic prediction algorithms remain insufficiently validated. To clarify this issue, we recruited 52 treatment-naïve, HIV-1-infected patients in Tanzania, where multiple HIV-1 non-B subtypes co-circulate. Sequence analysis of 93 infectious envelope clones isolated from their plasma viral RNA revealed the co-circulation of subtypes A1, C, D, and inter-subtype recombinant forms (isRFs). Phenotypic tropism assays revealed that lentivirus reporters pseudotyped with 75 (80.6%) and 5 (5.4%) envelope clones could establish infection toward U87.CD4 cells expressing CCR5 (R5) and CXCR4 (X4), respectively; whereas the remaining 13 (14%) clones could infect both cells. Genotypic analyses by widely used algorithms including V3 net charge, Geno2pheno, WebPSSM, and PhenoSeq showed that almost all phenotypic X4-tropic clones and only 15 of 75 phenotypic R5-tropic clones were concordantly predicted. However, the remaining 60 phenotypic R5-tropic clones were discordantly predicted by at least one algorithm. In particular, 2 phenotypic R5-tropic clones were discordantly predicted by all algorithms tested. Taken together, the results demonstrate the limitation of currently available genotypic algorithms for predicting co-receptor inference among co-circulating multiple non-B subtypes and emerging isRFs. Also, the phenotypic tropism dataset presented here could be valuable for retraining of the widely used genotypic prediction algorithms to enhance their performance. Frontiers Media S.A. 2021-07-07 /pmc/articles/PMC8292895/ /pubmed/34305873 http://dx.doi.org/10.3389/fmicb.2021.703041 Text en Copyright © 2021 Judicate, Barabona, Kamori, Mahiti, Tan, Ozono, Mgunya, Kuwata, Matsushita, Sunguya, Lyamuya, Tokunaga and Ueno. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Judicate, George P.
Barabona, Godfrey
Kamori, Doreen
Mahiti, Macdonald
Tan, Toong Seng
Ozono, Seiya
Mgunya, Amina Shaban
Kuwata, Takeo
Matsushita, Shuzo
Sunguya, Bruno
Lyamuya, Eligius
Tokunaga, Kenzo
Ueno, Takamasa
Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate
title Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate
title_full Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate
title_fullStr Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate
title_full_unstemmed Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate
title_short Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate
title_sort phenotypic and genotypic co-receptor tropism testing in hiv-1 epidemic region of tanzania where multiple non-b subtypes co-circulate
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292895/
https://www.ncbi.nlm.nih.gov/pubmed/34305873
http://dx.doi.org/10.3389/fmicb.2021.703041
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