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Dual R3R5 tropism characterizes cerebrospinal fluid HIV-1 isolates from individuals with high cerebrospinal fluid viral load

Karlsson, Ulf LU ; Antonsson, Liselotte LU ; Ljungberg, Bengt LU ; Medstrand, Patrik LU ; Esbjörnsson, Joakim LU ; Jansson, Marianne LU and Gisslen, Magnus (2012) In AIDS 26(14). p.1739-1744
Abstract
Objective: To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples. Design: Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression in the central nervous system (CNS). Methods: HIV-1 isolates obtained from plasma and CSF in 28 individuals with varying viral load, CD4(+) T-cell counts, and with or without AIDS-defining disease were analyzed for the ability to infect NP2.CD4 cells stably expressing a panel of HIV coreceptors (CCR5, CXCR4, CCR3, CXCR6, GPR1, APJ, ChemR23, RDC-1... (More)
Objective: To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples. Design: Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression in the central nervous system (CNS). Methods: HIV-1 isolates obtained from plasma and CSF in 28 individuals with varying viral load, CD4(+) T-cell counts, and with or without AIDS-defining disease were analyzed for the ability to infect NP2.CD4 cells stably expressing a panel of HIV coreceptors (CCR5, CXCR4, CCR3, CXCR6, GPR1, APJ, ChemR23, RDC-1 or BLT1). Results: All isolates from both plasma and CSF utilized CCR5 and/or CXCR4. However, the ability to use both CCR3 and CCR5 (R3R5) was more pronounced in CSF isolates and correlated with high CSF viral load and low CD4(+) T-cell count. Notably, four out of five CSF isolates of subtype C origin exhibited CXCR6 use, which coincided with high CSF viral load despite preserved CD4(+) T-cell counts. The use of other alternative coreceptors was less pronounced. Conclusion: Dual-tropic R3R5 HIV-1 isolates in CSF coincide with high CSF viral load and low CD4(+) T-cell counts. Frequent CXCR6 use by CSF-derived subtype C isolates indicates that subtype-specific differences in coreceptor use may exist that will not be acknowledged when assessing plasma virus isolates. The findings may also bare relevance for HIV-1 replication within the CNS, and consequently, for the neuropathogenesis of AIDS. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CCR3, cerebrospinal fluid viral load, CXCR6, HIV-1 R5, late stage, disease, subtype C
in
AIDS
volume
26
issue
14
pages
1739 - 1744
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000308683700002
  • pmid:22695299
  • scopus:84866317711
ISSN
1473-5571
DOI
10.1097/QAD.0b013e3283560791
language
English
LU publication?
yes
id
7bf7d077-651c-4cf5-8ac1-233e598d32a1 (old id 3191196)
date added to LUP
2012-12-03 07:11:01
date last changed
2017-01-01 04:10:04
@article{7bf7d077-651c-4cf5-8ac1-233e598d32a1,
  abstract     = {Objective: To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples. Design: Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression in the central nervous system (CNS). Methods: HIV-1 isolates obtained from plasma and CSF in 28 individuals with varying viral load, CD4(+) T-cell counts, and with or without AIDS-defining disease were analyzed for the ability to infect NP2.CD4 cells stably expressing a panel of HIV coreceptors (CCR5, CXCR4, CCR3, CXCR6, GPR1, APJ, ChemR23, RDC-1 or BLT1). Results: All isolates from both plasma and CSF utilized CCR5 and/or CXCR4. However, the ability to use both CCR3 and CCR5 (R3R5) was more pronounced in CSF isolates and correlated with high CSF viral load and low CD4(+) T-cell count. Notably, four out of five CSF isolates of subtype C origin exhibited CXCR6 use, which coincided with high CSF viral load despite preserved CD4(+) T-cell counts. The use of other alternative coreceptors was less pronounced. Conclusion: Dual-tropic R3R5 HIV-1 isolates in CSF coincide with high CSF viral load and low CD4(+) T-cell counts. Frequent CXCR6 use by CSF-derived subtype C isolates indicates that subtype-specific differences in coreceptor use may exist that will not be acknowledged when assessing plasma virus isolates. The findings may also bare relevance for HIV-1 replication within the CNS, and consequently, for the neuropathogenesis of AIDS. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins},
  author       = {Karlsson, Ulf and Antonsson, Liselotte and Ljungberg, Bengt and Medstrand, Patrik and Esbjörnsson, Joakim and Jansson, Marianne and Gisslen, Magnus},
  issn         = {1473-5571},
  keyword      = {CCR3,cerebrospinal fluid viral load,CXCR6,HIV-1 R5,late stage,disease,subtype C},
  language     = {eng},
  number       = {14},
  pages        = {1739--1744},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {AIDS},
  title        = {Dual R3R5 tropism characterizes cerebrospinal fluid HIV-1 isolates from individuals with high cerebrospinal fluid viral load},
  url          = {http://dx.doi.org/10.1097/QAD.0b013e3283560791},
  volume       = {26},
  year         = {2012},
}