The function of the N terminus of the murine leukemia virus (MuLV) surface
(SU) protein was examined. A series of five chimeric envelope proteins (Env
) were generated in which the N terminus of amphotropic 4070A was replaced
by equivalent sequences from ecotropic Moloney MuLV (M-MuLV). Viral titers
of these chimeras indicate that exchange with homologous sequences could be
tolerated, up to V17eco/T15ampho (crossover III). Constructs encoding the
first 28 amino acids (aa) of ecotropic M-MuLV resulted in Env expression an
d binding to the receptor; however, the virus titer was reduced 5- to 45-fo
ld, indicating a postbinding block. Additional exchange beyond the first 28
aa of ecotropic MuLV Env resulted in defective protein expression. These N
-terminal chimeras were also introduced into the AE4 chimeric Env backbone
containing the amphotropic receptor binding domain joined at the hinge regi
on to the ecotropic SU C terminus. In this backbone, introduction of the fi
rst 17 aa of the ecotropic Env protein significantly increased the titer co
mpared to that of its parental chimera AE4, implying a functional coordinat
ion between the N terminus of SU and the C terminus of the SU and/or transm
embrane proteins. These data functionally dissect the N-terminal sequence o
f the MuLV Env protein and identify differential effects on receptor-mediat
ed entry.