The R5 to X4 Coreceptor Switch

In this paper, we show how a game theoretic analysis can provide a model to explain the interdependence of host produced APOBEC3G levels and limited X4 transmission. From our analysis, we show that when APOBEC3G strongly favors mutation from an R5 strain to an X4 strain, it can be optimal for the HIV-1 virus to suppress transmission of the X4 variant, despite the loss of X4 fitness potential. This is particularly true when the X4 strain significantly interferes with the host adaptive immune response. Transmitting only R5 viruses has two advantages so far as HIV-1 is concerned. First, it allows for an increased host lifespan, since deadly viral loads will not be reached as rapidly with only one independently replicating strain. Second, R5 viruses can, as a result of under-repression of APOBEC3G, generate X4 viruses which interfere with immune defense. In contrast, X4 viruses do not have this capability, since they are already more A-rich than R5 viruses, and will only continue to progress towards an A-rich ceiling as a result of APOBEC3G action.