THE AMPBOTROPIC AND ECOTROPIC MURINE LEUKEMIA-VIRUS ENVELOPE TM SUBUNITS ARE EQUIVALENT MEDIATORS OF DIRECT MEMBRANE-FUSION - IMPLICATIONS FOR THE ROLE OF THE ECOTROPIC ENVELOPE AND RECEPTOR IN SYNCYTIUM FORMATION AND VIRAL ENTRY

The murine leukemia virus (MuLV) envelope protein was examined to dete rmine which sequences are responsible for the differences in direct me mbrane fusion observed with the ecotropic and amphotropic MuLV subtype s. These determinants were studied by utilizing amphotropic ecotropic chimeric envelope proteins that have switched their host range but ret ain their original fusion domain (TM subunit). Fusion was tested both in rodent cells and in 293 cells bearing the human homolog of the ecot ropic MuLV receptor. The results demonstrate that the amphotropic TM i s able to mediate cell-to cell fusion to an extent equivalent to that mediated by the ecotropic TM, indicating that their fusion domains are equivalent, The ''murinized'' human homolog of the ecotropic receptor supports syncytium formation as well as the native murine receptor. T hese findings suggest that interactions between the ecotropic envelope protein and conserved sequences in the ecotropic receptor are the pri ncipal determinants of syncytium formation. The relationship of the fu sion phenotype to pa-dependent infection and the route of viral entry was examined by studying virions bearing the chimeric envelope protein s. Such virions appear to enter cells via a pathway that is directed b y the host range determining region of their envelope rather than by s equences that confer pH dependence. Therefore, the pH dependence of in fection may not reflect the initial steps in viral entry. Thus, it app ears that both the syncytium phenotype and the route of viral entry ar e properties of the viral receptor, the amino-terminal half of the eco tropic envelope protein, or the interaction between the two.