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 and carboxy-terminal regions of HIV-1 Vif as being important for a Vif+ phenotype. Mutants in a residue (Trp21) near to the amino-terminus of Vif, which is conserved between HIV-1, HIV-2, and SIVmac, were generated in the permissive C8166 cell line, and their Vif phenotype determined by monitoring their growth on the nonpermissive H9 cell line. Of seven variants at position 21 of Vif only phenylalanine substituted successfully for Trp21. The expression of the mutant Vif proteins was shown to be similar to wildtype levels, 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 growth of virus in nonpermissive H9 cells, and suggest that there is limited scope for variation at this position of HIV-1 Vif.