CXCR4 overexpression during the course of HIV-1 infection correlates with the emergence of X4 strains.
The factors that determine the emergence of X4 isolates in some HIV-1-infected subjects are unknown. As the level of expression of CXCR4 could favor an R5 to X4 switch, quantitative flow cytometry was used to measure CXCR4 density on CD4 T cells in 200 HIV-1-positive adults, and this was compared with CD4 counts, interleukin-7 (IL-7), and RANTES (regulated on activation, normal T expressed and secreted) plasma levels and the R5/X4 virus phenotype. CD4 T-cell surface CXCR4 densities were increased in infected subjects and inversely correlated with CD4 T-cell count (r=-0.548, P<0.001). Yet, in vitro infection with either R5 or X4 strains and in vivo increases in viral load following interruption of antiretroviral treatment did not induce CXCR4 overexpression. The plasma levels of IL-7 and RANTES, 2 cytokines able to induce CXCR4 expression, did not correlate with CXCR4 density. Finally, higher CXCR4 densities were observed in patients harboring X4 strains (3300, 95% CI 2431-4169 CXCR4 molecules per cell) than in patients harboring only R5 strains (2406, 95% CI 2135-2677, P=0.027). These data suggest that CXCR4 overexpression during the course of the disease in some patients could favor the emergence of X4 strains.
Lin
Yea-Lih
YL
Institut de Génétique Humaine, Montpellier, France.
Portales
Pierre
P
Segondy
Michel
M
Baillat
Vincent
V
de Boever
Corinne Merle
CM
Le Moing
Vincent
V
Réant
Brigitte
B
Montes
Brigitte
B
Clot
Jacques
J
Reynes
Jacques
J
Corbeau
Pierre
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018946:Chemokine CCL5 / Q000097:blood; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000097:blood* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000097:blood; D019562:Viral Load; D014779:Virus Replication
D018946:Chemokine CCL5; D015851:Interleukin-7; D019718:Receptors, CXCR4