Chronic lymphocytic leukemia B cells are highly sensitive to infection by herpes simplex virus-1 via herpesvirus-entry-mediator A.
We found that chronic lymphocytic leukemic (CLL) B cells are highly sensitive to infection with vectors derived from replication-defective herpes simplex virus-1 (rdHSV-1). CLL B cells were found to express high levels of herpes virus entry mediator (Hve) A, but not HveC, the other known receptor for HSV-1. An HveA cDNA from CLL cells was found to encode Arg-->Lys and Val-->Iso substitutions at amino acids 17 and 241, respectively. Nevertheless, this cDNA encoded a functional receptor for HSV-1 when transfected into Chinese hamster ovarian (CHO) cells. Antibodies to HveA could block rdHSV-1 infection of CLL cells and HveA-transfected CHO cells with similar efficiencies in vitro. In contrast to B cells of normal donors, CLL B cells were resistant to the cytopathic effects of infection by rdHSV-1 and maintained high-level expression of the transgene for several days in vitro. We propose that this is due to the expression by CLL cells of the anti-apoptotic protein, bcl-2. Consistent with this, we found that transduction of HeLa cells with a retrovirus expression vector encoding bcl-2 rendered HeLa cells resistant to the cytopathic effects of rdHSV-1. HSV-1-derived vectors should be excellent vehicles for gene transfer into CLL B cells, allowing for its potential use in gene therapy for this disease. Gene Therapy (2000) 7, 1210-1216.
Eling
D J
DJ
Division of Hematology/Oncology, Department of Medicine, UCSD School of Medicine, La Jolla, CA 92093-0663, USA.
Johnson
P A
PA
Sharma
S
S
Tufaro
F
F
Kipps
T J
TJ
D000818:Animals; D002472:Cell Transformation, Viral; D002999:Clone Cells; D006224:Cricetinae; D005434:Flow Cytometry; D019254:Genes, bcl-2; D006561:Herpes Simplex / Q000201:enzymology / Q000235:genetics / Q000821:virology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000235:genetics / Q000821:virology*; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
D001616:beta-Galactosidase