New and novel intrinsic host repressive factors against HIV-1: PAF1 complex, HERC5 and others

The best characterized HIV restriction factors are encoded by the APOBEC3 and TRIM gene families. The interplay between these cellular and viral proteins appears to be an important factor in deciding the ultimate disease outcome. Interestingly, HIV has also armed itself to counter various cellular intrinsic defense mechanisms, thereby overcoming the intrinsic responses mounted by the host. Therefore, today there is an intense effort in the HIV/AIDS field to define both important host-encoded antiviral restriction factors and viral counter-defense mechanisms that play key roles in the pathogenesis. Along these lines, the list of both restriction factors (proteins that counter specific viral proteins) and repressive factors (inhibitors of HIV life cycle) has been growing continuously. These factors not only include APOBECs, TRIM5α, p21/waf1, and SAMHD1, which act on the incoming virus [1], but also TRIM22, TRIM28/KAP1, and BST2/Tetherin, which exert their effect on post integration, assembly and budding.In a recent manuscript by Liu et al., the authors utilized an siRNA screening method to knockdown expression of 19,121 human genes [2]. They specifically looked for knockdown of restriction factors that would rescue the early stages of HIV replication from post entry to integration. The assay utilized viral pseudotypes HIV89.6R and HIV8.2N which are capable of a single round of infection. To optimize the screening, they used negative control siRNAs targeting cyclophilin B, PLK1 and GFP in target HeLa-CD4 cells. They identified 114 genes that affected a wide range of cellular activities that could be classified as genes that defend against retroviral invasion. These factors fall into various functional categories such as receptor signaling, vesicle trafficking, transcription, mRNA processing, DNA/RNA surveillance, cross-nuclear membrane transport and ubiquitination. Interestingly, they did not observe the presence of the classical RNA-recognizing PRRs such as toll like