Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

The coevolution of human antiviral protein APOBEC3G and HIV protein Vif: A theoretical study
Akira Sasaki

Last modified: 2014-06-09


Apolipoprotein B mRNA-editing, catalytic polypeptide-like 3 G (A3G) is a key protein in  human innate immune defense against human immune deficiency virus-1 (HIV-1). It induces G-to-A hypermutation in HIV cDNA to stop the viral replication in the infected cell. A viral infectivity factor (Vif) of HIV-1 is a countermeasure against A3G by binding A3G, thereby rolling the viral mutation rate back to below the error threshold. A simple mathematical model for the coevolution of A3G and Vif expression levels predicts coevolutionary cycles that are made up of a phase of the co-escalation of A3G and Vif expression levels and a phase of their co-deceleration. In the co-escalation phase, the hosts tryto push up the viral mutation rate towards the error catastrophe by increasing A3G expression level, and viruses try to mitigate it by increasing Vif expression level. In the co-deceleration phase, the hosts try to pull down viral mutation rate to slow down the speed of the antigenic escape from immune response, and viruses try to enhance its mutability by decreasing Vif expression levels. We discuss the other coevolutionary outcomes and the condition for their occurrences in the parameter space. A more microscopic model for Vif expression regulation through the modification of multiple splicing rate is also discussed.