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  • Viral Transfer Technology
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Chronic lymphocytic leukemia B cells are highly sensitive to infection by herpes simplex virus-1 via herpesvirus-entry-mediator A

Gene Therapy volume 7, pages 1210–1216 (2000)Cite this article

Abstract

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.

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Acknowledgements

We greatly appreciate the anti-HveA polyreactive antibody provided to us by Patricia Spear. We also acknowledge Bill Wierda, Jan Burger, Astrid Sandoval and Patricia Diotto for their technical and writing assistance. This work was supported in part by National Institutes of Health grants R01CA66000–05 and R37CA49870–12.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, UCSD School of Medicine, La Jolla, CA, USA

    DJ Eling, S Sharma & TJ Kipps

  2. NeuroVir Therapeutics Inc., Vancouver, BC, Canada

    PA Johnson & F Tufaro

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  1. DJ Eling
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  3. S Sharma
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  4. F Tufaro
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Eling, D., Johnson, P., Sharma, S. et al. Chronic lymphocytic leukemia B cells are highly sensitive to infection by herpes simplex virus-1 via herpesvirus-entry-mediator A. Gene Ther 7, 1210–1216 (2000). https://doi.org/10.1038/sj.gt.3301241

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