Mode of Coreceptor Use by R5 HIV Type 1 Correlates with Disease Stage: A Study of Paired Plasma and Cerebrospinal Fluid Isolates.
(2009) In AIDS Research and Human Retroviruses 25(12). p.1297-1305- Abstract
- Abstract Through the use of chimeric CXCR4/CCR5 receptors we have previously shown that CCR5-tropic (R5) HIV-1 isolates acquire a more flexible receptor use over time, and that this links to a reduced viral susceptibility to inhibition by the CCR5 ligand RANTES. These findings may have relevance with regards to the efficacy of antiretroviral compounds that target CCR5/virus interactions. Compartmentalized discrepancies in coreceptor use may occur, which could also affect the efficacy of these compounds at specific anatomical sites, such as within the CNS. In this cross-sectional study we have used wild-type CCR5 and CXCR4 as well as chimeric CXCR4/CCR5 receptors to characterize coreceptor use by paired plasma and cerebrospinal fluid (CSF)... (More)
- Abstract Through the use of chimeric CXCR4/CCR5 receptors we have previously shown that CCR5-tropic (R5) HIV-1 isolates acquire a more flexible receptor use over time, and that this links to a reduced viral susceptibility to inhibition by the CCR5 ligand RANTES. These findings may have relevance with regards to the efficacy of antiretroviral compounds that target CCR5/virus interactions. Compartmentalized discrepancies in coreceptor use may occur, which could also affect the efficacy of these compounds at specific anatomical sites, such as within the CNS. In this cross-sectional study we have used wild-type CCR5 and CXCR4 as well as chimeric CXCR4/CCR5 receptors to characterize coreceptor use by paired plasma and cerebrospinal fluid (CSF) isolates from 28 HIV-1-infected individuals. Furthermore, selected R5 isolates, with varying chimeric receptor use, were tested for sensitivity to inhibition by the CCR5 antagonist TAK-779. Discordant CSF/plasma virus coreceptor use was found in 10/28 patients. Low CD4(+) T cell counts correlated strongly with a more flexible mode of R5 virus CCR5 usage, as disclosed by an increased ability to utilize chimeric CXCR4/CCR5 receptors, specifically receptor FC-2. Importantly, an elevated ability to utilize chimeric receptors correlated with a reduced susceptibility to inhibition by TAK-779. Our findings show that a discordant CSF and plasma virus coreceptor use is not uncommon. Furthermore, we provide support for an emerging paradigm, where the acquisition of a more flexible mode of CCR5 usage is a key event in R5 virus pathogenesis. This may, in turn, negatively impact the efficacy of CCR5 antagonist treatment in late stage HIV-1 disease. (Less)
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https://lup.lub.lu.se/record/1523675
- author
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- AIDS Research and Human Retroviruses
- volume
- 25
- issue
- 12
- pages
- 1297 - 1305
- publisher
- Mary Ann Liebert, Inc.
- external identifiers
-
- wos:000272608400013
- pmid:20001314
- scopus:73149096528
- pmid:20001314
- ISSN
- 1931-8405
- DOI
- 10.1089/aid.2009.0069
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Infection Medicine (SUS) (013008000), Reconstructive Surgery (013240300), Molecular Virology (013212007), Division of Medical Microbiology (013250400), Drug Target Discovery (013212045)
- id
- d511080f-dbc0-436a-910c-7a37f5c720e9 (old id 1523675)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20001314?dopt=Abstract
- date added to LUP
- 2016-04-04 07:50:25
- date last changed
- 2022-02-20 20:56:52
@article{d511080f-dbc0-436a-910c-7a37f5c720e9, abstract = {{Abstract Through the use of chimeric CXCR4/CCR5 receptors we have previously shown that CCR5-tropic (R5) HIV-1 isolates acquire a more flexible receptor use over time, and that this links to a reduced viral susceptibility to inhibition by the CCR5 ligand RANTES. These findings may have relevance with regards to the efficacy of antiretroviral compounds that target CCR5/virus interactions. Compartmentalized discrepancies in coreceptor use may occur, which could also affect the efficacy of these compounds at specific anatomical sites, such as within the CNS. In this cross-sectional study we have used wild-type CCR5 and CXCR4 as well as chimeric CXCR4/CCR5 receptors to characterize coreceptor use by paired plasma and cerebrospinal fluid (CSF) isolates from 28 HIV-1-infected individuals. Furthermore, selected R5 isolates, with varying chimeric receptor use, were tested for sensitivity to inhibition by the CCR5 antagonist TAK-779. Discordant CSF/plasma virus coreceptor use was found in 10/28 patients. Low CD4(+) T cell counts correlated strongly with a more flexible mode of R5 virus CCR5 usage, as disclosed by an increased ability to utilize chimeric CXCR4/CCR5 receptors, specifically receptor FC-2. Importantly, an elevated ability to utilize chimeric receptors correlated with a reduced susceptibility to inhibition by TAK-779. Our findings show that a discordant CSF and plasma virus coreceptor use is not uncommon. Furthermore, we provide support for an emerging paradigm, where the acquisition of a more flexible mode of CCR5 usage is a key event in R5 virus pathogenesis. This may, in turn, negatively impact the efficacy of CCR5 antagonist treatment in late stage HIV-1 disease.}}, author = {{Karlsson, Ulf and Antonsson, Liselotte and Repits, Johanna and Medstrand, Patrik and Owman, Christer and Kidd-Ljunggren, Karin and Hagberg, Lars and Svennerholm, Bo and Jansson, Marianne and Gisslén, Magnus and Ljungberg, Bengt}}, issn = {{1931-8405}}, language = {{eng}}, number = {{12}}, pages = {{1297--1305}}, publisher = {{Mary Ann Liebert, Inc.}}, series = {{AIDS Research and Human Retroviruses}}, title = {{Mode of Coreceptor Use by R5 HIV Type 1 Correlates with Disease Stage: A Study of Paired Plasma and Cerebrospinal Fluid Isolates.}}, url = {{http://dx.doi.org/10.1089/aid.2009.0069}}, doi = {{10.1089/aid.2009.0069}}, volume = {{25}}, year = {{2009}}, }