The helper virus envelope glycoprotein affects the disease specificity of a recombinant murine leukemia virus carrying a v-myc oncogene

Many retroviruses that carry oncogenes (acute transforming viruses) are gen erally replication-defective and therefore require co-infection with a repl ication competent 'helper' retrovirus for infectivity. The helper virus pro vides the retroviral proteins necessary for particle production and infecti on. These include the envelope glycoproteins that specifically bind to cell surface receptors and mediate viral adsorption and entry. Thus, a particul ar helper virus may influence the nature of disease induced by an oncogene- containing retrovirus due to tissue tropism of the helper. In a previous st udy, a replication-defective recombinant Moloney murine leukemia virus cont aining the v-myc oncogene was generated (M-MuLV(myc); Brightman B.K., Patte ngale P.K., and Fan H., J Virol 60: 68-81, 1986). When M-MuLV(myc) was inoc ulated into mice using the non-pathogenic amphotropic murine leukemia virus (Am-MuLV 4070) as a helper, T- and B-lymphoblastic lymphomas resulted with the following two surface phenotypes, namely, (1) Thy1.2+, B220- and (2) T hy1.2-, B220+. Thy 1.2 surface antigen is characteristic of cells of the ly mphoid lineage, whereas B220 surface antigen is characteristic of cells of the B-lymphoid lineage. In these experiments, to assess the influence of th e helper virus on the disease specificity of M-MuLV(myc), two weakly pathog enic ecotropic helper MuLVs that interact with different cell surface recep tors than Am-MuLV (Mo+PyFl0l and AKV MuLV) were used to pseudotype M-MuLV(m yc). In both cases, when inoculated into mice, these pseudotypes induced on ly T-lymphoblastic lymphoma. These results indicate that for M-MuLV(myc) th e types of the tumors induced are influenced by the helper virus utilized, and they suggest that different lymphoid cells may express different levels of retroviral receptors.