Identification of a functionally important amino acid residue near to the amino-terminus of the human immunodeficiency virus type 1 Vif protein

Previous studies have reported the importance of residues in the central an d carboxy-terminal regions of HIV-1 Vif as being important for a Vif(+) phe notype. Mutants in a residue (Trp21) near to the amino-terminus of Vif, whi ch is conserved between HIV-1, HIV-2, and SIVmac, were generated in the per missive C8166 cell line, and their Vif phenotype determined by monitoring t heir growth on the nonpermissive H9 cell line. Of seven variants at positio n 21 of Vif only phenylalanine substituted successfully for Trp21. The expr ession of the mutant Vif proteins was shown to be similar to wildtype level s, in C8166 cells, in all cases except one. These data identify Trp21 as an amino-terminal residue which is important to Vif function, in allowing gro wth of virus in nonpermissive H9 cells, and suggest that there is limited s cope for variation at this position of HIV-1 Vif.