Figure 6: A proposed model for ASK1 enhancement of the antiviral activity of A3G.
From: ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction
For efficient viral replication, Vif targets A3G for ubiquitination and proteasomal degradation by forming a stem cell factor-like E3 ubiquitin ligase complex composed of CUL5, ELOB/C and CBFβ. External agents such as AZT can induce ASK1 expression. ASK1 physically interacts with Vif and interferes with the formation of the Vif–E3 ubiquitin ligase complex. Consequently, the antiviral activity of A3G is restored and the virus replication is inhibited. Although another HIV accessory protein, Nef, inhibits the kinase activity of ASK1, this protein does not appear to alter the impact of ASK1 on Vif.
