INFECTION OF HUMAN ENDOTHELIAL-CELLS WITH EPSTEIN-BARR-VIRUS

Interleukin-6 (IL-6) promotes growth and tumorigenicity of Epstein-Bar r virus (EBV)-immortalized B cells, and is abnormally elevated in the serum of solid organ transplant recipients who develop EBV-positive po sttransplant lymphoproliferative disease (PTLD), but not in control tr ansplant recipients. Endothelial cells derived from PTLD lesions were found to secrete spontaneously high levels of IL-6 in vitro for up to 4 mo. We examined possible mechanisms for sustained IL-6 production by endothelial cells. Here, we show that EBV can infect endothelial cell s in vitro. After 3-4 wk incubation with lethally irradiated EBV-posit ive, but not EBV-negative cell lines, a proportion of human umbilical cord-derived endothelial cells (HUVECs) expressed in situ the EBV-enco ded small RNAs (EBER). Southern blot analysis after polymerase chain r eaction showed EBV DNA in HUVEC that had been incubated with lethally irradiated EBV-positive cells, but not in the controls. Exposure of HU VECs to lethally irradiated EBV-positive but not EBV-negative cell lin es induced IL-6 production that was sustained for up to 120 d of cultu re. These studies identify endothelial cells as targets for EBV infect ion and raise the possibility that this infection may be important in the life cycle and pathology of EBV.