Lentivirus restriction by diverse primate APOBEC3A proteins

• Virus restriction by human APOBEC3A can be restored with 6 amino acid substitutions from rhesus APOBEC3A.
• Virus restriction of simian human immunodeficiency virus by APOBEC3A is conserved among old world primates.
• The APOBEC3A from Colobus guereza restricts virus replication by a novel mechanism.

Rhesus macaque APOBEC3A (rhA3A) is capable of restricting both simian–human immunodeficiency virus (SHIVΔvif) and human immunodeficiency virus (HIV-1Δvif) to a greater extent than hA3A. We constructed chimeric A3A proteins to define the domains required for differential lentivirus restriction. Substitution of amino acids 25–33 from rhA3A into hA3A was sufficient to restrict HIVΔvif to levels similar to rhA3A restriction of SHIVΔvif. We tested if differential lentivirus restriction is conserved between A3A from Old World monkey and hominid lineages. A3A from African green monkey restricted SHIVΔvif but not HIV-1Δvif and colobus monkey A3A restricted both wild type and SHIVΔvif and HIV-1Δvif. In contrast, the gibbon ape A3A restricted neither SHIVΔvif nor HIV-1Δvif. Restriction of SHIVΔvif and HIV-1Δvif by New World monkey A3A proteins was not conserved as the A3A from the squirrel monkey but not the northern owl monkey restricted SHIVΔvif. Finally, the colobus A3A protein appears to restrict by a novel post-entry mechanism.