Advanced

Coevolution of RANTES sensitivity and mode of CCR5 receptor use by human immunodeficiency virus type 1 of the R5 phenotype.

Karlsson, Ingrid LU ; Antonsson, Liselotte LU ; Shi, Yu; Öberg, Monica LU ; Karlsson, Anders; Albert, Jan; Olde, Björn LU ; Owman, Christer LU ; Jansson, Marianne LU and Fenyö, Eva Maria LU (2004) In Journal of Virology 78(21). p.11807-11815
Abstract
The evolution of human immunodeficiency virus type 1 (HIV-1) coreceptor use has been described as the acquisition of CXCR4 use linked to accelerated disease progression. However, CXCR4-using virus can be isolated only from approximately one-half of individuals with progressive HIV-1 disease. The other half continue to yield only CCR5-using viruses (R5 phenotype) throughout the course of disease. In the present work, the use of receptor chimeras between CCR5 and CXCR4 allowed us to study the evolution of HIV-1 with the R5 phenotype, which was not revealed by studies of wild-type coreceptor use. All together, 246 isolates (173 with the R5 phenotype) from 31 individuals were tested for their ability to infect cells through receptor chimeras.... (More)
The evolution of human immunodeficiency virus type 1 (HIV-1) coreceptor use has been described as the acquisition of CXCR4 use linked to accelerated disease progression. However, CXCR4-using virus can be isolated only from approximately one-half of individuals with progressive HIV-1 disease. The other half continue to yield only CCR5-using viruses (R5 phenotype) throughout the course of disease. In the present work, the use of receptor chimeras between CCR5 and CXCR4 allowed us to study the evolution of HIV-1 with the R5 phenotype, which was not revealed by studies of wild-type coreceptor use. All together, 246 isolates (173 with the R5 phenotype) from 31 individuals were tested for their ability to infect cells through receptor chimeras. R5narrow virus was able to use only wild-type CCR5, whereas R5broad(1) to R5broad(3) viruses were able to use one to three chimeric receptors, respectively. Broad use of chimeric receptors was interpreted as an increased flexibility in the mode of receptor use. R5broad isolates showed higher infectivity in cells expressing wild-type CCR5 than R5narrow isolates. Also, the increased flexibility of R5broad isolates was concomitant with a lower sensitivity to inhibition by the CC chemokine RANTES. Our results indicate a close relationship between HIV-1 phenotypic changes and the pathogenic process, since the mode and efficiency of CCR5 use as well as the decrease in the RANTES sensitivities of isolated viruses are significantly correlated with CD4+-T-cell decline in a patient. One possible explanation is that ligand competition at the CCR5 receptor or changed CCR5 availability may shape the outcome of HIV-1 infection. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Virology
volume
78
issue
21
pages
11807 - 11815
publisher
American Society for Microbiology
external identifiers
  • wos:000224540900035
  • scopus:6344237375
ISSN
1098-5514
DOI
10.1128/JVI.78.21.11807-11815.2004
language
English
LU publication?
yes
id
47802826-54a1-4e41-be50-bf90243c8121 (old id 129812)
date added to LUP
2007-07-10 07:19:35
date last changed
2017-10-08 04:21:58
@article{47802826-54a1-4e41-be50-bf90243c8121,
  abstract     = {The evolution of human immunodeficiency virus type 1 (HIV-1) coreceptor use has been described as the acquisition of CXCR4 use linked to accelerated disease progression. However, CXCR4-using virus can be isolated only from approximately one-half of individuals with progressive HIV-1 disease. The other half continue to yield only CCR5-using viruses (R5 phenotype) throughout the course of disease. In the present work, the use of receptor chimeras between CCR5 and CXCR4 allowed us to study the evolution of HIV-1 with the R5 phenotype, which was not revealed by studies of wild-type coreceptor use. All together, 246 isolates (173 with the R5 phenotype) from 31 individuals were tested for their ability to infect cells through receptor chimeras. R5narrow virus was able to use only wild-type CCR5, whereas R5broad(1) to R5broad(3) viruses were able to use one to three chimeric receptors, respectively. Broad use of chimeric receptors was interpreted as an increased flexibility in the mode of receptor use. R5broad isolates showed higher infectivity in cells expressing wild-type CCR5 than R5narrow isolates. Also, the increased flexibility of R5broad isolates was concomitant with a lower sensitivity to inhibition by the CC chemokine RANTES. Our results indicate a close relationship between HIV-1 phenotypic changes and the pathogenic process, since the mode and efficiency of CCR5 use as well as the decrease in the RANTES sensitivities of isolated viruses are significantly correlated with CD4+-T-cell decline in a patient. One possible explanation is that ligand competition at the CCR5 receptor or changed CCR5 availability may shape the outcome of HIV-1 infection.},
  author       = {Karlsson, Ingrid and Antonsson, Liselotte and Shi, Yu and Öberg, Monica and Karlsson, Anders and Albert, Jan and Olde, Björn and Owman, Christer and Jansson, Marianne and Fenyö, Eva Maria},
  issn         = {1098-5514},
  language     = {eng},
  number       = {21},
  pages        = {11807--11815},
  publisher    = {American Society for Microbiology},
  series       = {Journal of Virology},
  title        = {Coevolution of RANTES sensitivity and mode of CCR5 receptor use by human immunodeficiency virus type 1 of the R5 phenotype.},
  url          = {http://dx.doi.org/10.1128/JVI.78.21.11807-11815.2004},
  volume       = {78},
  year         = {2004},
}