Figure 1

Schematic illustration of the action of host restriction factors during primate lentivirus replication. In viral producer cells, both A3 and MOV10 proteins are packaged into virions via interaction with Gag and RNA. A3 proteins can be targeted by Vif for proteasomal degradation, and viral RNAs can be targeted by specific microRNAs (miRNAs) for suppression. Vpx is also packaged into virion via direct interaction with Gag. In addition, viral release can be inhibited by the cell surface protein tetherin, but it is counteracted by Vpu or Nef (not shown). In target cells, TRIM5α interacts with incoming Gag proteins and triggers premature viral uncoating, resulting in inhibition of viral reverse transcription and nuclear import. Reverse transcription can also be directly inhibited by MOV10 and A3 proteins, or indirectly by SAMHD1 after depleting intracellular dNTP pool. However, SAMHD1 can be neutralized by Vpx through proteasomal degradation. In addition, A3 proteins catalyze C-to-U cytidine deamination on newly synthesized viral cDNA, and viral RNAs can be targeted by miRNAs, which also result in inhibition of viral replication.