Pathogenesis and virus content of lymphomas induced by pure ecotropic graffi murine leukemia virus

Abstract

Tumors induced by wild type Graffi murine leukemia virus (Gi-MuLV) contained high titers of MuLV consisting of a predominant ecotropic (e)-MuLV and a scarcer titer recombinant (RM) MuLV component. Each of these was purified by biological cloning and examined for its envelope properties and leukemogenicity. Both the e- and the RM-MuLV's were single isolates and unique in terms of their neutralization profiles and peptide maps. The cloned e-Gi-MuLV was highly leukemogenic in C57B1 mice, inducing a very rapid lethal thymic lymphoma but no myeloid leukemia. e-Gi-MuLV also accelerated thymic lymphoma in AKR mice. The purified RM-MuLV did not induce any tumors. Infectious cell center (ICC) experiments of organs of mice inoculated with e-Gi-MuLV showed that virus replicated very rapidly and reached maximal titers in about one week in C57B1 mice. There was a highly preferential replication in the thymus of the animal so that this e-Gi-MuLV can be considered as thymotropic. Within two weeks after infection of mice, infected cells of the thymus also began to release low levels of a non-ecotropic MuLV. The rapid induction of lymphoma is compared to that induced by other e-MuLV's and their RM-MuLV's, and to the natural AKR-MuLV-associated disease. These findings are discussed in the context of prevailing theories on envelope gene rearrangements in the virus and in the proviral sequences in resulting tumors.