The mouse genome contains various genes which are involved in virus-induced neoplastic disease. These genes include endogenous retroviral sequences as well as mouse cellular genes which facilitate or restrict virus replication. Various cellular genes can also function as viral receptors; we used the human gene for the gibbon ape leukemia virus (GALV) receptor to identify and map homologous sequences to mouse chromosome 2, suggesting a possible identity with Rec-2, the chromosome 2 encoded receptor for a wild mouse retrovirus; we also identified multiple copies of GALV-related sequences in the mouse genome suggesting that this gene may have functioned as a receptor during the evolution of Mus. In other experiments we identified several novel common viral integration regions associated with tumor induction. Two integration regions for BL/LV3 radiation leukemia virus were mapped to opposite ends of mouse chromosome 6. One of the common integration sites for Friend MuLV mapped near the protooncogene locus Kras-2, and a second Friend site maps at or near the Fv-2 resistance gene. In order to determine the possible identity of these genes we mapped both in the same genetic cross. These experiments produced a molecular genetic map around the Fv-2 locus and failed to provide evidence that the two may be distinct loci. Finally, we have used site specific mutagenesis to alter the site in the CAgag region of the AKV MuLV which is thought to interact with the gene product of the Fv-1 resistance gene. Results show that only a single amino acid substitution is sufficient to alter virus tropism. Other changes were introduced into this site, some of which did not alter virus replication patterns, some of which converted the original N-tropic virus into a characteristic B-tropic virus, and one of which produced a virus with a novel replication pattern on cells derived from various inbred strains and wild mouse species.
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