Lentivirus restriction by diverse primate APOBEC3A proteins

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• APOBEC3A (A3A) proteins are key antiviral factors.
• Rhesus macaque APOBEC3A (rhA3A) exhibits potent restriction of simian-human immunodeficiency virus (SHIV) and human immunodeficiency virus (HIV).
• Understanding the molecular basis of differential lentivirus restriction by A3A proteins is crucial.

Purpose of the Study:

• To identify the domains within rhA3A responsible for its enhanced lentivirus restriction.
• To investigate the conservation of differential lentivirus restriction across primate A3A orthologs.
• To explore the mechanism of restriction employed by colobus monkey A3A.

Main Methods:

• Construction and analysis of chimeric A3A proteins.
• Testing A3A orthologs from various primate species for restriction of SHIVΔvif and HIV-1Δvif.
• Investigating the mechanism of action for colobus monkey A3A.

Main Results:

• Substitution of amino acids 25-33 from rhA3A into human A3A (hA3A) conferred enhanced restriction of HIVΔvif.
• A3A proteins from Old World monkeys (African green monkey, colobus monkey) showed varying degrees of SHIVΔvif and HIV-1Δvif restriction.
• Gibbon ape A3A and New World monkey A3A proteins exhibited limited or no restriction of these lentiviruses.
• Colobus monkey A3A demonstrated a novel post-entry restriction mechanism.

Conclusions:

• The N-terminal domain of rhA3A, specifically amino acids 25-33, is critical for enhanced lentivirus restriction.
• Differential lentivirus restriction by A3A orthologs is not universally conserved across primate lineages.
• Colobus monkey A3A employs a unique post-entry antiviral strategy.