Figure 2: Mechanism of action of APOBEC3 (A3) and Vif in the HIV-1 life cycle. At the top panel, a virus-producing cell in the absence (left) or in the presence (right) of a functional Vif protein is shown. In the presence of Vif (orange rectangle), A3 (blue ellipse) is primarily targeted to proteasomal degradation (1); Vif can also block A3 mRNA translation (2) and prevent A3 packaging into the virion in a degradation-independent manner (3). In the absence of Vif, A3 molecules are packaged into incoming virus particles. After a new infection (bottom panel), A3 exerts its antiviral activity in multiple ways. A3 can interfere with reverse transcription in a deamination-independent manner (1). A3 can also interfere with proviral integration through the formation of abnormal viral DNA ends (2). In the hypermutation process, A3 mainly deaminates dC residues in the negative strand of the complementary viral DNA, originating dU, that serves as template for the incorporation of dA in the positive strand. If able to integrate, hypermutated proviruses are normally largely defective (3). Alternatively, viral DNA containing multiple dU can also be degraded before integration (4).