Infection of human endothelial cells with Epstein-Barr virus.
Interleukin-6 (IL-6) promotes growth and tumorigenicity of Epstein-Barr virus (EBV)-immortalized B cells, and is abnormally elevated in the serum of solid organ transplant recipients who develop EBV-positive posttransplant lymphoproliferative disease (PTLD), but not in control transplant 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 cells in vitro. After 3-4 wk incubation with lethally irradiated EBV-positive, but not EBV-negative cell lines, a proportion of human umbilical cord-derived endothelial cells (HUVECs) expressed in situ the EBV-encoded small RNAs (EBER). Southern blot analysis after polymerase chain reaction showed EBV DNA in HUVEC that had been incubated with lethally irradiated EBV-positive cells, but not in the controls. Exposure of HUVECs to lethally irradiated EBV-positive but not EBV-negative cell lines induced IL-6 production that was sustained for up to 120 d of culture. These studies identify endothelial cells as targets for EBV infection and raise the possibility that this infection may be important in the life cycle and pathology of EBV.
Jones
K
K
Division of Hematologic Products, Food and Drug Administration, Bethesda, Maryland, USA.
Rivera
C
C
Sgadari
C
C
Franklin
J
J
Max
E E
EE
Bhatia
K
K
Tosato
G
G
D001483:Base Sequence; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D004730:Endothelium, Vascular / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D016867:Immunocompromised Host; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000821:virology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications / Q000209:etiology / Q000821:virology*; D014180:Transplantation; D014471:Umbilical Veins; D014764:Viral Proteins / Q000032:analysis; D014779:Virus Replication
D016207:Cytokines; D004279:DNA, Viral; D015850:Interleukin-6; D014764:Viral Proteins