HIV-1 induction of CD40 on endothelial cells promotes the outgrowth of AIDS-associated B-cell lymphomas

Ashlee V. Moses, Sally E. Williams, Joanne G. Strussenberg, Marika L. Heneveld, Rebecca A. Ruhl, Antony C. Bakke, Grover C. Bagby, Jay A. Nelson

Research output: Contribution to journalArticle

47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1242-1249
Number of pages8
JournalNature medicine
Volume3
Issue number11
DOIs
StatePublished - Nov 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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