title: Interleukin-7 in plasma correlates with CD4 T-cell depletion and may be associated with emergence of syncytium-inducing variants in human immunodeficiency virus type 1-positive individuals.
abstract: Human immunodeficiency virus type 1 (HIV-1) primary infection is characterized by the use of CCR5 as a coreceptor for viral entry, which is associated with the non-syncytium-inducing (NSI) phenotype in lymphoid cells. Syncytium-inducing (SI) variants of HIV-1 appear in advanced stages of HIV-1 infection and are characterized by the use of CXCR4 as a coreceptor. The emergence of SI variants is accompanied by a rapid decrease in the number of T cells. However, it is unclear why SI variants emerge and what factors trigger the evolution of HIV from R5 to X4 variants. Interleukin-7 (IL-7), a cytokine produced by stromal cells of the thymus and bone marrow and by keratin, is known to play a key role in T-cell development. We evaluated IL-7 levels in plasma of healthy donors and HIV-positive patients and found significantly higher levels in HIV-positive patients. There was a negative correlation between circulating IL-7 levels and CD4(+) T-cell count in HIV-positive patients (r = -0.621; P < 0.001), suggesting that IL-7 may be involved in HIV-induced T-cell depletion and disease progression. IL-7 levels were higher in individuals who harbored SI variants and who had progressed to having CD4 cell counts of lower than 200 cells/microl than in individuals with NSI variants at a similar stage of disease. IL-7 induced T-cell proliferation and up-regulated CXCR4 expression in peripheral blood mononuclear cells in vitro. Taken together, our results suggest a role for IL-7 in the maintenance of T-cell regeneration and depletion by HIV in infected individuals and a possible relationship between IL-7 levels and the emergence of SI variants.
authors.affiliation: Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Llano
authors.forename: J
authors.initials: J
authors.lastname: Barretina
authors.forename: A
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: J
authors.initials: J
authors.lastname: Blanco
authors.forename: C
authors.initials: C
authors.lastname: Cabrera
authors.forename: B
authors.initials: B
authors.lastname: Clotet
authors.forename: J A
authors.initials: JA
authors.lastname: Esté
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D015497:HIV-1 / Q000145:classification*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood* / Q000502:physiology; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015415:Biomarkers; D015851:Interleukin-7; D019718:Receptors, CXCR4