A role for type I interferons in the resistance of chronic lymphocytic leukemia to vesicular stomatitis virus

Abstract

Vesicular Stomatitis Virus (VSV) is a naturally oncolytic agent that is exquisitely sensitive to the antiviral effects of Type I Interferons (IFN). Although 81% of human cancer cell lines in the NCI-60 panel are sensitive to VSV, Chronic Lymphocytic Leukemia (CLL), the most common adult leukemia in the West, is resistant. It is hypothesized that this resistance is due to an intact IFN pathway in CLL cells. A quantitative PCR based approach was taken to examine the IFN gene expression profile of CLL cells. It was discovered that CLL cells constitutively express IFNbeta and IFNalphaR1 transcripts which may contribute to an inherent antiviral state in these cells. However, upon activation of CLL cells, IFN transcript levels decrease and susceptibility to VSV infection is increased. As complete sensitivity to VSV is not achieved, the contribution of other antiviral mechanisms cannot be excluded. Understanding the mechanisms of viral resistance in CLL and uncovering novel approaches of manipulating them will have future implications for VSV therapy of CLL.