Inhibition of HIV-1 Vif by Pokeweed Antiviral Protein and its Impact on Cellular Immune Defense

Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like editing complex 3G (APOBEC3G) is a DNA editing enzyme. APOBEC3G hypermutates human immunodeficiency virus type 1 (HIV-1) DNA, resulting in the inhibition of viral propagation. The HIV-1 accessory protein viral infectivity factor (Vif) targets APOBEC3G for degradation. The objective of this work was to evaluate whether the inhibitory effect of Vif on A3G can be diminished by pokeweed antiviral protein (PAP). PAP is an N-glycosidase synthesized by the pokeweed plant, Phytolacca americana. In this study, I show that PAP reduced Vif protein accumulation by depurinating Vif open reading frame (ORF). Decreased Vif protein levels in the presence of PAP were correlated with increased A3G levels. The antiviral enzyme reduced viral particle release by approximately 100-fold and the virions released from PAP expressing cells were 11-fold less infectious. The expression of PAP also reduced the levels of integrated HIV-1 DNA.