title: HIV-1 induction of CD40 on endothelial cells promotes the outgrowth of AIDS-associated B-cell lymphomas.
abstract: Human immunodeficiency virus (HIV)-1 infection is associated with the development of aggressive extranodal B-cell non-Hodgkin's lymphomas. Using microvascular endothelial cell (MVEC)-enriched bone marrow stromal cultures, HIV infection of stromal MVECs from lymphoma patients induced the outgrowth of malignant B cells. MVECs were the only HIV-infected cells in the stroma, and purified brain MVECs also induced a phenotype supportive of neoplastic B-cell attachment and proliferation. HIV infection of MVECs stimulated surface expression of CD40 and allowed preferential induction of the vascular cell adhesion molecule VCAM-1 after CD40 triggering. B-lymphoma cells expressed the CD40 ligand (CD40L), and blocking of CD40-CD40L interactions between HIV-infected MVECs and B-lymphoma cells inhibited B-cell attachment and proliferation. These observations suggest that HIV promotes B-lymphoma cell growth through facilitating attachment of lymphoma cells to HIV-infected MVECs and represent a novel mechanism through which viruses may induce malignancies.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201-3011, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Moses
authors.forename: S E
authors.initials: SE
authors.lastname: Williams
authors.forename: J G
authors.initials: JG
authors.lastname: Strussenberg
authors.forename: M L
authors.initials: ML
authors.lastname: Heneveld
authors.forename: R A
authors.initials: RA
authors.lastname: Ruhl
authors.forename: A C
authors.initials: AC
authors.lastname: Bakke
authors.forename: G C
authors.initials: GC
authors.lastname: Bagby
authors.forename: J A
authors.initials: JA
authors.lastname: Nelson
mesh_terms: D019013:CD40 Antigens / Q000096:biosynthesis* / Q000378:metabolism; D023201:CD40 Ligand; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000276:immunology*; D005434:Flow Cytometry; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D023201:CD40 Ligand