Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen

TLDR

HIV‑1 exploits multiple host proteins during infection. We performed a large‑scale small interfering RNA screen to identify host factors required by HIV‑1. The screen identified more than 250 HIV‑dependency factors (HDFs). The screen uncovered over 250 host dependency factors involved in diverse cellular functions, including novel roles for retrograde Golgi transport proteins in entry, a karyopherin in integration, and the Mediator complex in transcription, with many factors highly expressed in immune cells, demonstrating the utility of RNAi and forward genetics for revealing HIV dependencies and therapeutic targets.

Abstract

HIV-1 exploits multiple host proteins during infection. We performed a large-scale small interfering RNA screen to identify host factors required by HIV-1 and identified more than 250 HIV-dependency factors (HDFs). These proteins participate in a broad array of cellular functions and implicate new pathways in the viral life cycle. Further analysis revealed previously unknown roles for retrograde Golgi transport proteins (Rab6 and Vps53) in viral entry, a karyopherin (TNPO3) in viral integration, and the Mediator complex (Med28) in viral transcription. Transcriptional analysis revealed that HDF genes were enriched for high expression in immune cells, suggesting that viruses evolve in host cells that optimally perform the functions required for their life cycle. This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy.