Mechanism of interaction between endogenous ecotropic murine leukemia viruses in (BALB/c × C57BL/6) hybrid cells

Abstract

The germline ecotropic murine leukemia (MuLV) proviruses of BALB/c and C57BL/6 (B6) mice were analyzed to determine the molecular basis of low virus expression in these mouse strains and to determine the mechanism of interaction of these two proviruses. Previous work had demonstrated that the BALB/c endogenous ecotropic provirus was infectious but unable to induce XC cell syncytia formation, and that induced (BALB/c × B6) hybrid cells expressed 10- to 50-fold more XC syncytia than induced parental cells. Two independently isolated DNA clones of the 136 endogenous ecotropic provirus were noninfectious following transfection into cells, and cell lines that expressed this viral genome produced noninfectious MuLV. Nucleotide sequencing of the mutant region of the B6 provirus indicated that the defective nature of this provirus resulted from an amino acid substitution of proline for alanine in the central portion of reverse transcriptase. From the analysis of the virus produced by induced hybrid cells, and the patterns of steady-state viral RNA in induced cells, we propose that the enhanced XC cell syncytia formation observed in hybrid cells is due to trans-complementation of viral proteins and not viral recombination or trans-activation of viral genome expression.