Fig. 1

The HIV-1 genome and strategies for antiviral targeting. a Structure of the HIV-1 genome. The genome contains nine genes and two long terminal repeats (LTRs) that can be targeted by RNA interference (RNAi). Certain genomic regions are more conserved than others, making them better targets. In addition, many of the genes are alternatively spliced, requiring careful target design. b HIV-1 targeting. Several steps of the HIV-1 viral replication cycle can be targeted by RNAi. Current drug targets are in parentheses. (1) The first step is receptor binding and membrane fusion by the HIV envelope glycoproteins gp120 and gp41 to host receptors CD4 and either CCR5 or CXCR4. This step can be inhibited by knocking down the HIV-1 co-receptors, CCR5 or CXCR4. (2) Next, the viral genome must be reverse transcribed by the viral reverse transcriptase (RT) and (3) integrated into the cellular genome which is mediated by the viral integrase protein and host factors LEDGF, Importin, and Chaperonin. After integration, (4) the virus is transcribed, which is mediated by viral (TAR and tat) and host (pTEFb, tat-SF1, SPT5, cyclin T1) factors, (5) exported to the cytoplasm (dependent on DDX3 and Rev) and then translated and (6) subjected to post-translational processing by the viral protease. (7) Finally, the proteins are processed and (8) packaged into new viral particles