HIV-1 induction of CD40 on endothelial cells promotes the outgrowth of AIDS-associated B-cell lymphomas.
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.
Moses
A V
AV
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201-3011, USA.
Williams
S E
SE
Strussenberg
J G
JG
Heneveld
M L
ML
Ruhl
R A
RA
Bakke
A C
AC
Bagby
G C
GC
Nelson
J A
JA
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
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D023201:CD40 Ligand