The Dileucine-Based Sorting Motif in HIV-1 Nef Is Not Required for Down-Regulation of Class I MHC

• Published in: Virology (New York, N.Y.) Vol. 258; no. 2; pp. 203 - 207
• Main Authors: Riggs, Nanette L., Craig, Heather M., Pandori, Mark W., Guatelli, John C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05-06-1999
• Subjects: Binding Sites; Cell Line; Down-Regulation; Gene Products, nef - genetics; Gene Products, nef - immunology; Gene Products, nef - metabolism; HIV-1 - immunology; HLA-A2 Antigen - biosynthesis; Human immunodeficiency virus 1; Humans; Leucine - genetics; Leucine - immunology; Leucine - metabolism; Mutagenesis, Site-Directed; nef Gene Products, Human Immunodeficiency Virus; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1999.9736

A dileucine-based protein sorting motif has recently been identified within the C-terminal, solvent-exposed loop of HIV-1 Nef and has been shown to be required for Nef-mediated down-regulation of CD4 and for optimal viral infectivity. Here, we report that mutation of the dileucine motif has no effect on Nef-mediated down-regulation of class I MHC heavy chain. Instead, deletion of an acidic domain just N-terminal of the polyproline helix of the SH3-binding domain significantly impairs this function. These data indicate that down-regulation of class I MHC and CD4 are mechanistically distinct processes. The data also suggest that protein interactions mediated by the acidic domain, rather than by the dileucine motif, may contribute to this function of Nef.