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R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies

Entry coreceptor use by HIV-1 plays a pivotal role in viral transmission, pathogenesis and disease progression. In many HIV-1 infected individuals, there is an expansion in coreceptor use from CCR5 to include CXCR4, which is associated with accelerated disease progression. While targeting HIV-1 enve...

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Autores principales: Loftin, Lamorris M, Kienzle, Martha, Yi, Yanjie, Collman, Ronald G
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105503/
https://www.ncbi.nlm.nih.gov/pubmed/21284902
http://dx.doi.org/10.1186/1479-5876-9-S1-S3
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author Loftin, Lamorris M
Kienzle, Martha
Yi, Yanjie
Collman, Ronald G
author_facet Loftin, Lamorris M
Kienzle, Martha
Yi, Yanjie
Collman, Ronald G
author_sort Loftin, Lamorris M
collection PubMed
description Entry coreceptor use by HIV-1 plays a pivotal role in viral transmission, pathogenesis and disease progression. In many HIV-1 infected individuals, there is an expansion in coreceptor use from CCR5 to include CXCR4, which is associated with accelerated disease progression. While targeting HIV-1 envelope interactions with coreceptor during viral entry is an appealing approach to combat the virus, the methods of determining coreceptor use and the changes in coreceptor use that can occur during disease progression are important factors that may complicate the use of therapies targeting this stage of HIV-1 replication. Indicator cells are typically used to determine coreceptor use by HIV-1 in vitro, but the coreceptors used on these cells can differ from those used on primary cell targets. V3 based genetic sequence algorithms are another method used to predict coreceptor use by HIV-1 strains. However, these algorithms were developed to predict coreceptor use in cell lines and not primary cells and, furthermore, are not highly accurate for some classes of viruses. This article focuses on R5X4 HIV-1, the earliest CXCR4-using variants, reviewing the pattern of coreceptor use on primary CD4+ lymphocytes and macrophages, the relationship between primary cell coreceptor use and the two principal approaches to coreceptor analysis (genetic prediction and indicator cell phenotyping), and the implications of primary cell coreceptor use by these strains for treatment with a new class of small molecule antagonists that inhibit CCR5-mediated entry. These are important questions to consider given the development of new CCR5 blocking therapies and the prognosis associated with CXCR4 use.
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spelling pubmed-31055032011-06-02 R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies Loftin, Lamorris M Kienzle, Martha Yi, Yanjie Collman, Ronald G J Transl Med Review Entry coreceptor use by HIV-1 plays a pivotal role in viral transmission, pathogenesis and disease progression. In many HIV-1 infected individuals, there is an expansion in coreceptor use from CCR5 to include CXCR4, which is associated with accelerated disease progression. While targeting HIV-1 envelope interactions with coreceptor during viral entry is an appealing approach to combat the virus, the methods of determining coreceptor use and the changes in coreceptor use that can occur during disease progression are important factors that may complicate the use of therapies targeting this stage of HIV-1 replication. Indicator cells are typically used to determine coreceptor use by HIV-1 in vitro, but the coreceptors used on these cells can differ from those used on primary cell targets. V3 based genetic sequence algorithms are another method used to predict coreceptor use by HIV-1 strains. However, these algorithms were developed to predict coreceptor use in cell lines and not primary cells and, furthermore, are not highly accurate for some classes of viruses. This article focuses on R5X4 HIV-1, the earliest CXCR4-using variants, reviewing the pattern of coreceptor use on primary CD4+ lymphocytes and macrophages, the relationship between primary cell coreceptor use and the two principal approaches to coreceptor analysis (genetic prediction and indicator cell phenotyping), and the implications of primary cell coreceptor use by these strains for treatment with a new class of small molecule antagonists that inhibit CCR5-mediated entry. These are important questions to consider given the development of new CCR5 blocking therapies and the prognosis associated with CXCR4 use. BioMed Central 2011-01-27 /pmc/articles/PMC3105503/ /pubmed/21284902 http://dx.doi.org/10.1186/1479-5876-9-S1-S3 Text en Copyright ©2011 Loftin et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Loftin, Lamorris M
Kienzle, Martha
Yi, Yanjie
Collman, Ronald G
R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies
title R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies
title_full R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies
title_fullStr R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies
title_full_unstemmed R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies
title_short R5X4 HIV-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies
title_sort r5x4 hiv-1 coreceptor use in primary target cells: implications for coreceptor entry blocking strategies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105503/
https://www.ncbi.nlm.nih.gov/pubmed/21284902
http://dx.doi.org/10.1186/1479-5876-9-S1-S3
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