Differential disease restriction of Moloney and Friend murine leukemia viruses by the mouse Rmcf gene is governed by the viral long terminal repeat.

Abstract

Neonatal CxD2 (Rmcfr) and Balb/c (Rmcfs) mice inoculated with Moloney murine leukemia virus (M-MuLV) exhibited approximately equivalent time course and pathology for disease. CxD2 mice showed only slightly reduced presence of Moloney mink cell focus-forming virus (M-MCF) provirus as seen by Southern blot analysis compared to Balb/c mice. This lack of restriction for disease and spread of MCF was in sharp contrast to that seen for CxD2 mice inoculated with Friend murine leukemia virus (F-MuLV), where incidence of disease and propagation of MCFs were severely restricted, as previously reported. Inoculation of CxD2 mice with FM-MuLV, a recombinant F-MuLV virus containing M-MuLV LTR sequences (U3 and R), resulted in T cell disease of time course equal to that seen in Balb/c mice; there also was little restriction for propagation of MCFs. This indicated that presence of the M-MuLV long terminal repeat (LTR) was sufficient for propagation of MCFs in CxD2 mice. Differing restriction for F-MuLV vs. M-MuLV in CxD2 mice was explained on the basis of different "MCF propagator cells" for the two viruses. It was suggested that cells propagating F-MCF (e.g., erythroid progenitors) are blocked by endogenous MCF-like gp70env protein, whereas cells propagating M-MCF (e.g., lymphoid) do not express this protein on their surface. F-MuLV disease in CxD2 mice was greatly accelerated when neonates were inoculated with a F-MuLV/F-MCF pseudotypic mixture. However, F-MCF provirus was not detectable or only barely detectable in F-MuLV/F-MCF-induced tumors, suggesting that F-MCF acted indirectly in induction of these tumors.