APOBEC3G: a double agent in defense

APOBEC3G (A3G) is an effective cellular host defense factor under experimental conditions in which a functional form of the HIV-encoded protein Vif cannot be expressed. Wild-type Vif targets A3G for proteasomal degradation and when this happens, any host defense advantage A3G might provide is severely diminished or lost. Recent evidence cast doubt on the potency of A3G in host defense and suggested that it could, under some circumstances, promote the emergence of more virulent HIV strains. In this article, I suggest that it is time to recognize that A3G has the potential to act as a double agent. Future research should focus on understanding how cellular and viral regulatory mechanisms enable the antiviral function of A3G, and on the development of novel research reagents to explore these pathways.