title: High CD4(+) T-cell surface CXCR4 density as a risk factor for R5 to X4 switch in the course of HIV-1 infection.
abstract: For unclear reasons, about 50% of HIV-infected subjects harbour CXCR4-using (X4) viral strains in addition of CCR5-using (R5) viral strains at late stages of the disease. One hypothesis is that a low CD4(+) T-cell surface CCR5 density could facilitate the emergence of X4 strains. Alternatively, one could argue that a high CD4(+) T-cell surface CXCR4 density that is observed in individuals presenting with X4 strains, could favour R5 to X4 switch. Here, we tested both hypotheses. In vivo, we observed by quantitative flow cytometry no difference in CD4(+) T-cell surface CCR5 densities between patients with or without X4 strains. In the course of an in vitro R5 infection, the delay of emergence of X4 mutants was similar between cells expressing 2 distinct cell surface CCR5 densities, but shorter (12 ± 0 days and 21 ± 0 days, respectively, P = 0.01) in cells expressing a high surface CXCR4 density as compared with cells with a low surface CXCR4 density. These data argue for a role of CXCR4 density, but not of CCR5 density, in the emergence of X4 strains. They are reassuring concerning the risk of inducing an R5 to X4 switch using CCR5 antagonists to treat HIV infection.
authors.affiliation: Institut de Génétique Humaine, CNRS UPR1142, Montpellier, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Fiser
authors.forename: Thierry
authors.initials: T
authors.lastname: Vincent
authors.forename: Natalie
authors.initials: N
authors.lastname: Brieu
authors.forename: Yea-Lih
authors.initials: YL
authors.lastname: Lin
authors.forename: Pierre
authors.initials: P
authors.lastname: Portalès
authors.forename: Clément
authors.initials: C
authors.lastname: Mettling
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.forename: Pierre
authors.initials: P
authors.lastname: Corbeau
mesh_terms: D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D005260:Female; D005434:Flow Cytometry; D015752:Genes, env; D057809:HEK293 Cells; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019713:Receptors, CCR5 / Q000032:analysis* / Q000276:immunology; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000276:immunology; D017384:Sequence Deletion; D014779:Virus Replication
chemical_list: D000954:Antigens, Surface; C527276:CXCR4 protein, human; D019713:Receptors, CCR5; D019718:Receptors, CXCR4