A single dominant gene determines susceptibility to a leukaemogenic recombinant retrovirus

The production of recombinant retroviruses is an important episode in the natural history of thymic leukaemia in AKR and HRS/J (hr/hr) mices. These viruses apparently originate from ecotropic and xenotropic precursors in the late preleukaemic stage of the disease. Analyses of their structural proteins and genomic oligonucleotides indicate that they arise by recombination of env genes of the precursor viruses. This event leads to a viral envelope glycoprotein (gp70) with some peptides that have features of the gp70 glycoproteins of ecotropic and xenotropic viruses, and others that are unique for each recombinant virus. The former property explains the broad host range of recombinant viruses, and hence their designation as dual tropic or polytropic viruses. It has been postulated that the unique aspect of each recombinant's gp70 determines the phenotypes of leukaemic cells. Polytropic viruses may be highly thymotropic. Their systemic administration results in an infection that confines itself virtually to the thymus. Moreover, these viruses are leukaemogenic whereas their precursors are not, or only weakly so. The leukaemogenicity of polytropic viruses is, however, restricted to certain inbred strains of mice. The HRS/J isolate PTV-1 is leukaemogenic in HRS/J and CBA/J mice, but not in SWR/J or NIH/Swiss mice. The experiments described here demonstrate that a single dominant gene permits infection by thymocytes by a leukaemogenic polytrophic virus. CBA/J mice, which develop thymic leukaemia after infection by this virus, posesses this gene, whereas leukaemia-resistant NFS mice lack it.