title: CD40-activated macrophages become highly susceptible to X4 strains of human immunodeficiency virus type 1.
abstract: Activating cells of the immune system may stimulate human immunodeficiency virus type 1 (HIV-1) replication and contribute to select pathogenic variants in vivo. Here, we examined the possible effect of a major pathway of immune activation, CD40 interaction with its ligand (CD40L), on the susceptibility of monocyte-derived macrophages (MDMs) to various HIV-1 strains. Stimulation of MDMs with CD40L led to reduced replication of R5 HIV-1(Ba-L), whereas this strongly enhanced the replication of X4 HIV-1(Lai) as well as of X4 primary isolates, and this was associated with strong cytopathic effects. The replication of X4 strains was inhibited by stromal cell-derived factor 1, an indication of the restricted usage of CXCR4 as virus coreceptor in this case. CD40L induced the activation of mitogen-activated protein kinases ERK1/ERK2 and stimulated MDMs to secrete RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, interleukin 6 (IL-6), IL-1beta, and tumor necrosis factor alpha. From this data, it may be hypothesized that activated macrophages represent a favorable environment for the replication of classically T lymphocyte-tropic X4 variants and, thus, may contribute significantly to the selection of such variants at late stages of clinical HIV-1 infection.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale EPI-0013, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 75571 Paris Cedex 12, France. ybakari@hotmail.com
authors.forename: Youssef
authors.initials: Y
authors.lastname: Bakri
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Mannioui
authors.forename: Loyda
authors.initials: L
authors.lastname: Ylisastigui
authors.forename: Françoise
authors.initials: F
authors.lastname: Sanchez
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Gluckman
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Benjouad
mesh_terms: D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010641:Phenotype; D014779:Virus Replication
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D023201:CD40 Ligand; D020928:Mitogen-Activated Protein Kinases