The gp52 envelope glycoprotein of the replication defective spleen focus-forming virus (SFFV) is responsible for the acute erythroleukemia inducing properties of this virus. gp52 is the product of a recombinant envelope gene that shows substitutions, deletions and insertions when compared to related murine leukemia virus (MuLV) envelope genes. We propose to investigate the role of each of these changes, found in SFFV gp52, in its leukemogeneicity. Available evidence indicates that multiple domains of SFFV gp52 are involved in leukemogeneicity. We will construct mutants of the SFFV envelope gene which express gp52- related molecules with an altered external domain, transmembrane domain or cytoplasmic domain, and investigate their leukemogeneicity as well as the ability of mutant gp52 molecules to mediate other changes observed in mice early during SFFV infection. We will investigate the effects of mutant gp52 molecules on the proliferation and differentiation of hemopoietic stem cells, erythroid burst-forming cells (BFU-E) or erythroid colony-forming cells (CFU-E) and the erythroprotein responsiveness of these cells. gp52 is defective in its transport to the cell surface and shows an unstable association with membrane. A small proportion of gp52 is expressed on the cell surface in polycythemia-inducing strains of SFFV, but not anemia- inducing strains of SFFV. We will investigate the membrane association and transport properties of the mutants to determine the structural features of gp52 responsible for its transport defects and altered subcellular localization patterns. We will also investigate the cellular mechanisms involved in the defective transport of SFFV gp52. Unlike MuLV envelope proteins, pg52 is not incorporated into the virus particles. We will investigate whether any of the mutant gp52 molecules are incorporated into the virus particles. These studies will provide information on the role of different domains of SFFV gp52 in mediating different in vivo effects of SFFV. Also, these studies will define the structural features of this viral glycoprotein that determine transport, sorting and assembly of these molecules into virus particles.
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