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UBC Theses and Dissertations

Characterization of an alphaherpesvirus resistant cell line Banfield, Bruce William

Abstract

A mouse L cell mutant termed gro29 has been isolated (Tufaro et al. 1987) and shown to be defective in the growth of two enveloped viruses, vesicular stom- atitis virus (VSV) and herpes simplex virus type 1 (HSV-1). In this thesis it is demonstrated that the rate of transport and processing of HSV-1 glycoproteins was impeded in infected gro29 cells. In addition, HSV-1 virions failed to exit the cell and accumulated in cytoplasmic vacuoles. The phenotype of the uninfected gro29 cell was examined. It was determined that gro29 cells were resistant to the lectins ricin and modeccin, and showed a reduced ability to bind fluorescently conjugated ricin. In addition, gro29 cells failed to synthesize the glycosaminoglycan chondroitin sulfate. The lectin binding properties of gro29 cells and the glycosaminoglycan synthesis profile exhibited by these cells suggested that gro29 might have suffered a defect in the metabolism of N- acetylgalactosamine (GalNAc). The metabolism of GalNAc was examined in gro29 cells and macromolecules directly involved in the synthesis and utilization of this molecule were found to be normal. The phenotype of gro29 suggested that HSV-1 requires a host cell component for efficient virus maturation and egress distinct from those components which facilitate the trafficking of viral membrane glycoproteins such as VSV G protein. The results presented in this thesis suggest that it may be possible to interfere with cell secretion or GalNAc metabolism such as to leave the cell viable yet impair the ability of cells to propagate herpes simplex virus.

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