Analysis of the N-terminal positively charged residues of the simian immunodeficiency virus Vif reveals a critical amino acid required for the antagonism of rhesus APOBEC3D, G, and H

•We mutated positively charged amino acid at the amino terminus of the SIV Vif.•The lysine at position 27 of the SIV Vif was important for antagonism of rhesus APOBEC3G and APOBEC3F.•The arginine at position 14 of the SIV Vif was important for antagonism of rhesus APOBEC3DE, G and F.

Previous studies have shown that apolipoprotein B mRNA editing, enzyme catalytic, polypeptide G (APOBEC3G; hA3G) and F (APOBEC3F; hA3F) proteins interact with a nonlinear binding site located at the N-terminal region of the HIV-1 Vif protein. We have analyzed the role of 12 positively charged amino acids of the N-terminal region of the SIV Vif. Simian-human immunodeficiency viruses (SHIV) were constructed that expressed each of these amino acid substitutions. These viruses were examined for replication in the presence of rhesus macaque APOBEC3 proteins (rhA3A-rhA3H), incorporation of the different A3 proteins into virions, and replication in rhesus macaque PBMC. Similar to other studies, we found that K27 was essential for rhA3G activity and rhA3F but was not important for restriction of SHIVΔvif by rhA3A, rhA3D or rhA3H. Our results identified the arginine at position 14 of the SIV Vif as a critical residue for virus restriction by rhA3D, rhA3G and rhA3H.