During the past year we have continued our studies of the regulation of retrotransposition/retrovirus integration. Our studies have focused on three areas. First, we have completed the development of a retrovirus packaging/vector system in which integration is restricted in mouse cells expressing the Fv-1b allele but not the Fv-1n allele. This is a unique system with which to study the mechanism by which the mouse Fv-1 gene product inhibits retrovirus DNA synthesis/maturation or integration into chromosomal DNA. Vector/packaging systems with different Fv-1 allele sensitivities are under construction. Secondly, we have analyzed the viral determinant for Fv-1b tropism. Our evidence suggests that this is a property of a moderately abundant family (approximately 30 members) of endogenous MuLV-related proviral genomes. Thus, in mice carrying the Fv-1b allele, selection against the Fv-1n tropism determinant of endogenous ecotropic MuLV results in the acquisition of the 8-tropic determinant from this more abundant class of endogenous sequences. Thirdly, in collaboration with Dr. Anton Jetten, LPP/NIEHS, we have begun a study of the regulation of the Fv-1 gene. Cell cultures derived from a common progenitor have been identified in which the Fv-1 gene is phenotypically silent in some clones and expressed in other clones. Preliminary evidence suggests that this will provide a model system for further analysis of the Fv-1 gene, including molecular cloning.
