First Name:
Corianne
Last Name:
Rogers
Major Department:
Biology
Thesis Director:
Maryam Ahmed
Date of Thesis:
May 2012
Vesicular stomatitis virus(VSV) is currently being studied as an oncolytic agent for the treatment of a variety of cancers. An important correlate of anti-tumor activity is the stimulation of natural killer (NK) cells, a specially type of lymphocyte. To determine the ability of VSV to activate NK cells, the natural killer cell line NK-92MI was infected with recombinant wild-type (rwt) and matrix (M) protein mutant (rM5IR-M) strains of VSV. rwt virus is a potent inhibitor of host gene expression, including expression of genes in the type I interferon (IFN) antiviral responses. rM51R-M virus is defective at inhibition of host gene expression and up-regulates the type IFN response. Because type I IFNs (IFNα and β) are important in stimulating NK cells, we hypothesized that rM51R-M virus would more effectively induce NK cell activation than rwt virus. Our results showed that both rwt and rM51R-M virus replicated to similar levels in NK-92MI cells. However, rM51R-M virus induced greater expression of IFN-γ than rwt virus in NK-92MI cells, as indicated by ELISA. rM51R-M virus infected NK cells also promoted the killing of tumor cells as compared to mock-infected cells. Further studies showed that when peripheral blood mononuclear cells (PBMCs) containing NK cells and other immune cell populations were infected with rM51R-M virus, there was increased expression of the inflammatory cytokines, IL-6 and TNFα as opposed to infections with rwt virus. Overall, these results indicate that rM51R-M virus is more successful at stimulating immune cells than rwt virus and may serve as an effective oncolytic agent to induce anti-tumor immunity during therapies.