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Bovine herpesvirus type 1 as a novel oncolytic virus

Cancer Gene Therapy volume 17, pages 344–355 (2010)Cite this article

Abstract

Oncolytic virotherapy is a promising avenue of cancer gene therapy. Current vectors include human viruses that have been engineered to replicate in tumor cells or nonhuman viruses that are naturally oncotropic and preferentially replicate in tumor cells harboring defects in innate immune pathways such as the type 1 interferon (IFN) pathway. Bovine herpesvirus type 1 (BHV-1) is a species-specific herpesvirus closely related to the human herpes simplex virus type 1 (HSV-1). Although BHV-1 does not efficiently replicate in and affect cellular viability of normal human cells, it is capable of infecting and killing various immortalized and transformed human cell types. Surprisingly, BHV-1 infection of human cells fails to elicit IFN production at the mRNA or protein level and the ability of BHV-1 to kill immortalized and transformed human cells does not correlate with defects in IFN pathways. Furthermore, although some cross-reactivity between BHV-1 and HSV-1 exists, the majority of human antibody or serum samples tested failed to neutralize BHV-1 despite possessing HSV-1 neutralizing capacity. Thus, BHV-1 is a novel candidate oncolytic virus with a distinct mechanism of tumor targeting.

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Acknowledgements

We thank V Misra, I Fidler, J Gauldie, G Kiel and B Lichty for reagents and D Cummings for technical assistance. RMR was supported by an Ontario Graduate Scholarship. KLM was the recipient of an R&D Health Research Career Award. This work was supported by operating grants from the Ontario Institute for Cancer Research and the Canadian Breast Cancer Foundation.

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Authors and Affiliations

  1. Department of Biochemistry and Biomedical Sciences, Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada

    R Rodrigues & K Mossman

  2. Department of Pathology and Molecular Medicine, Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada

    B Cuddington & K Mossman

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  1. R Rodrigues
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  3. K Mossman
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Correspondence to K Mossman.

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Rodrigues, R., Cuddington, B. & Mossman, K. Bovine herpesvirus type 1 as a novel oncolytic virus. Cancer Gene Ther 17, 344–355 (2010). https://doi.org/10.1038/cgt.2009.77

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