AbstractsBiology & Animal Science

Feline leukemia virus (FeLV) subgroups can be categorized based on their specific receptor usage. The transmissible form of FeLV is minimal pathogenic and is the parental form of the virus from which the other three subgroups are derived. While the cellular receptor used by the three of the four FeLV subgroups have been cloned and thoroughly characterized, the FeLV-A subgroup cellular receptor has remained elusive.The focus of this thesis has been the identification of the host cellular receptor utilized by the FeLV-A virus. The work presented here details the cloning and isolation of a feline protein that is shown to act as a viral receptor for FeLV-A. We find that the human ortholog of this feline protein is also capable of being used by FeLV-A to infect normally resistant murine cells.We have also investigated the normal cellular function of the host protein in addition to characterizing its viral receptor activity. The work presented shows that like the human orthologue, the feline cellular receptor functions as a thiamine transport protein. Additionally, we cloned and characterized a second feline thiamine transport protein, which we show does not function as a FeLV viral receptor but does have thiamine transporter capabilities.In a final set of experiments, we show that these two feline thiamine transporters differ not only in their ability to mediate FeLV-A infection, but also exhibit a different expression profile in various feline cellular compartments. We found that infection with FeLV-A in a feline fibroblast cell line, disrupted thiamine transport. Additionally, cells that have reduced thiamine uptake exhibit reduced growth and cellular death when grown in low concentrations of thiamine. Together, the work presented in this thesis suggest that specific interactions between the FeLV-A envelope and its cellular receptor effect not only thiamine transporter function but appears to have a significant pathogenic effect on cells in vitro. Whether the reduced thiamine transporter function seen during FeLV infection, in vivo, may be relevant to the connections between viral receptors and pathogenesis and future work will be needed to further investigate the potential mechanisms in FeLV-A viral receptor-mediated pathogenesis.