Generation of recombinant murine leukemia viruses de novo: an alternative model for leukemogenesis

Evidence for the viral etiology of murine lymphoma is very complex. Although ecotropic viruses were considered in the past to be the causative agents, envelope gene recombinant (RM) types of murine leukemia virus (MuLV) seem to be the best candidates at present. The following factors are relevant in the murine model: Pure ecotropic MuLV causes disease but induces RM-MuLV de novo in every case. RM-MuLV can cause disease in pure form. However, the mere presence of RM-MuLV may not be sufficient to cause disease in some cases. Ecotropic MuLV is needed under natural conditions for inducing T-cell blastogenesis, donating its coat to recombinant MuLV, and to become a partial parent for RM-MuLV. Early elimination of ecotropic MuLV can prevent disease. In a number of virus-free mouse lymphomas, the only indicator of virus involvement was on RM-MuLV glycoprotein on cell surface. Based on the above, a signal hypothesis model is proposed which attempts to integrate the above observations.