A single dominant gene determines susceptibility to a leukaemogenic recombinant retrovirus

Abstract

The production of recombinant retroviruses is an important episode in the natural history of thymic leukaemia in AKR and HRS/J (hr/hr) mice^1,2. These viruses apparently originate from ecotropic and xenotropic precursors in the late preleukaemic stage of the disease. Analyses of their structural proteins^3,4 and genomic oligonucleotides^3,5 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^3,4,6. The former property explains the broad host range of recombinant viruses, and hence their designation as dual tropic¹ or polytropic² viruses. It has been postulated that the unique aspect of each recombinant's gp70 determines the phenotypes of leukaemic cells⁷. Polytropic viruses may be highly thymotropic. Their systemic administration results in an infection that confines itself virtually to the thymus^3,8. Moreover, these viruses are leukaemogenic whereas their precursors are not, or only weakly so^3,8,9. The leukaemogenicity of polytropic viruses is, however, restricted to certain inbred strains of mice^3,8. The HRS/J isolate PTV-1 is leukaemogenic in HRS/J and CBA/J mice, but not in SWR/J or NIH/Swiss mice³. The experiments described here demonstrate that a single dominant gene permits infection of thymocytes by a leukaemogenic polytropic virus. CBA/J mice, which develop thymic leukaemia after infection by this virus, posesses this gene, whereas leukaemia-resistant NFS mice lack it.