Identification of vesicular stomatitis virus as a leukemolytic agent

In the course of tumourigenesis the interferon-response pathway is frequently disrupted. We have demonstrated that this common deficiency makes malignant cells highly susceptible to infection and killing by vesicular stomatitis virus (VSV). VSV is a an enveloped, negativestranded RNA virus which is known to be exquisitively sensitive to interferon. While VSV replication is blocked in normal cells by interferon the virus grows rapidly in tumour cells in the presence of interferon. Bone marrow cells are highly resistant to infection and killing by VSV. Infection of bone marrow with VSV at a multiplicity of infection (MOI) of 10 plaque forming units (PFU)/cell did not lead to viral replication, cell killing or a reduction in progenitor numbers even in the absence of exogenous interferon. Infection of leukemic cells, however leads to rapid viral replication, spread and killing. VSV is able to purge a normal bone marrow of OCI/AML3 cells following overnight infection while having no significant impact on the numbers of normal colony forming cells. We have demonstrated that AML cell lines and patient samples are susceptible to infection and killing by VSV. As well, we have preliminary evidence that CML, myeloma and ALL cells are also susceptible to VSV infection. In summary, while bone marrow cells are highly resistant to VSV many leukemic cells are susceptible to infection and killing by this virus.