Enhanced expression of the CXCR4 co-receptor in HIV-1-infected individuals correlates with the emergence of syncytia-inducing strains.
The aim of this study was to investigate the mechanisms responsible for the emergence in some HIV-1-infected individuals of highly aggressive, syncytia-inducing (SI) HIV-1 strains, which have been shown to use CXCR4 as co-receptor to enter target cells. To this end, the percentages of circulating CXCR4+CD4+ T cells were evaluated by flow cytometry in 39 untreated and 61 highly active antiretroviral therapy (HAART)-treated HIV-1-infected individuals in comparison with 35 HIV-1 seronegative subjects. Plasma viremia was also measured, and HIV primary isolates, from both untreated and HAART-treated HIV-1-infected subjects, were tested for the presence of SI strains. The results of this study showed enhanced proportions of CXCR4+CD4+ T cells in untreated patients in comparison with HAART-treated and healthy subjects. Furthermore, the results of a 12-month longitudinal study in a cohort of 11 patients undergoing HAART showed a significant reduction of CXCR4 expression after successful therapy. Finally, a significant positive correlation among the proportions of circulating CXCR4-expressing CD4+ T cells, plasma viremia, and the probability to isolate SI strains was found. These in vivo data are in keeping with previous in vitro results suggesting a bidirectional link between HIV-1 and CXCR4 expression on CD4+ T cells, and provide some clues to understanding the mechanisms exerting a selective pressure toward the emergence of SI strains.
Manetti
R
R
Department of Internal Medicine, University of Florence, Italy.
Cosmi
L
L
Galli
G
G
Annunziato
F
F
Mazzetti
M
M
Romagnani
S
S
Maggi
E
E
D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015726:Giant Cells / Q000821:virology*; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D018023:HIV Seronegativity; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D019562:Viral Load; D014766:Viremia / Q000821:virology
D019718:Receptors, CXCR4