Expression of chemokine receptors CXCR4 and CCR5 in HIV-1-infected and uninfected individuals.
The chemokine receptors CXCR4 and CCR5 have been identified as major coreceptors for HIV-1 entry into CD4+ T cells. The majority of primary HIV-1 isolates in early disease use CCR5 as a coreceptor, whereas during disease progression with the emergence of syncytium-inducing viruses, CXCR4 is also used. We performed a cross-sectional study in which we evaluated the expression of two HIV-1 coreceptors, CCR5 and CXCR4, in whole blood samples taken from HIV-1-infected and uninfected individuals. We demonstrate that CXCR4 on CD4+ and CD8+ T cells, and CD14+ monocytes is significantly down-regulated, and CCR5 expression on CD4+ T cells is up-regulated in HIV-infected individuals compared with uninfected controls. Coreceptor expression correlated with the level of cellular activation in vivo in both HIV-infected and uninfected individuals, with CXCR4 being expressed predominantly on quiescent (HLA-DR-) T cells and CCR5 being expressed predominantly on activated (HLA-DR+) T cells. Lower expression of CXCR4 and higher expression of CCR5 on CD4+ T cells correlated with advancing disease. In addition, a tendency for greater activation of CXCR4+CD4+ T cells in patients with advanced disease was observed. Patients who harbored syncytium-inducing viruses, however, could not be distinguished from those who harbored nonsyncytium-inducing viruses based on the level of CD4+ T cell activation or chemokine receptor expression.
Ostrowski
M A
MA
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-1576, USA. mostrowski@nih.gov
Justement
S J
SJ
Catanzaro
A
A
Hallahan
C A
CA
Ehler
L A
LA
Mizell
S B
SB
Kumar
P N
PN
Mican
J A
JA
Chun
T W
TW
Fauci
A S
AS
D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000097:blood; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology
D019713:Receptors, CCR5; D019718:Receptors, CXCR4