HIV-1 infection of microvascular endothelial cells facilitates growth of aids associated b cell lymphomas

A. V. Moses, M. Heneveld, J. A. Nelson, G. G. Bagby

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AIDS patients have a high incidence of aggressive B cell nonHodgkin's lymphomas (AIDS-NHL) that involve extranodal sites including bone marrow. Since malignant B cells in AIDS-NHL are not directly infected by HIV, interaction of B cells with HIV-infected accessory cells at extranodal sites may contribute to development and unique localization of such lymphomas. Using bone marrow stromal cultures enriched for microvascular endothelial cells (MVEC), we have demonstrated that bone marrow MVEC are naturally infected by HIV in vivo. (Moses A.V. et al. Blood, 1996). MVEC-enriched stromal culture derived from an HIV-seropositive patient with EBV-negative Burkitt's lymphoma gave rise to the spontaneous and sustained in vitro outgrowth of stromal dependent B cells containing the Burkitt's t(8;14) translocation. Moreover, ex vivo HIV infection of MVEC-enriched stroma from HIV-seronegative lymphoma patients induced outgrowths of autologous malignant B cells. We also found that adherence of B lymphoma cells to brain MVEC was significantly enhanced upon HIV infection and that while antibody blocking experiments demonstrated that the VCAM-1/VLA-4 interaction was involved, HIV infection of MVEC had no effect on the expression of VCAM1. However, while brain MVEC expressed CD40 at low levels constitutively, HIV infection significantly enhanced CD40 expression and, more importantly, an agonistic CD40 monoclonal antibody (mAb) triggered expression of VCAM-1 on infected brain MVEC but not mock-infected MVEC We suggest that HIV infection of MVEC in extranodal sites may be uniquely supportive of adhesion and outgrowth of lymphoma cells, in part, through a mechanism involving first induction of CD40 in MVEC by HIV-1 and secondly CD40L induced VCAM-1 expression by these cells.

Original languageEnglish (US)
Pages (from-to)732
Number of pages1
JournalExperimental hematology
Issue number8
StatePublished - 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research


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