The dileucine-based sorting motif in HIV-1 Nef is not required for down-regulation of class I MHC

dileucine-based protein sorting motif has recently been identified within t he C-terminal, solvent-exposed loop of HIV-1 Nef and has been shown to be r equired for Nef-mediated down-regulation of CD4 and for optimal viral infec tivity. Here, we report that mutation of the dileucine motif has no effect on Nef-mediated down-regulation of class I MHC heavy chain. Instead, deleti on of an acidic domain just N-terminal of the polyproline helix of the SH3- binding domain significantly impairs this function. These data indicate tha t down-regulation of class I MHC and CD4 are mechanistically distinct proce sses. The data also suggest that protein interactions mediated by the acidi c domain, rather than by the dileucine motif, may contribute to this functi on of Nef. (C) 1999 Academic Press.