The amphotropic 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 determine which sequences are responsible for the differences in direct membrane fusion observed with the ecotropic and amphotropic MuLV subtypes. These determinants were studied by utilizing amphotropic-ecotropic chimeric envelope proteins that have switched their host range but retain their original fusion domain (TM subunit). Fusion was tested both in rodent cells and in 293 cells bearing the human homolog of the ecotropic MuLV receptor. The results demonstrate that the amphotropic TM is 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. These findings suggest that interactions between the ecotropic envelope protein and conserved sequences in the ecotropic receptor are the principal determinants of syncytium formation. The relationship of the fusion phenotype to pH-dependent infection and the route of viral entry was examined by studying virions bearing the chimeric envelope proteins. Such virions appear to enter cells via a pathway that is directed by the host range-determining region of their envelope rather than by sequences that confer pH dependence. Therefore, the pH dependence of infection may not reflect the initial steps in viral entry. Thus, it appears that both the syncytium phenotype and the route of viral entry are properties of the viral receptor, the amino-terminal half of the ecotropic envelope protein, or the interaction between the two.
D016475:3T3 Cells; D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D015726:Giant Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009052:Leukemia Virus, Murine / Q000145:classification / Q000472:pathogenicity / Q000502:physiology*; D046911:Macromolecular Substances; D008561:Membrane Fusion; D051379:Mice; D011991:Receptors, Virus / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors; D014162:Transfection; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000502:physiology*
D046911:Macromolecular Substances; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins