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      Identification of host proteins required for HIV infection through a functional genomic screen.

      Science (New York, N.Y.)

      Cell Line, Tumor, Computational Biology, Cytoskeletal Proteins, genetics, physiology, Genomics, HIV Infections, metabolism, virology, HIV-1, pathogenicity, Host-Pathogen Interactions, Human Immunodeficiency Virus Proteins, Humans, Intracellular Signaling Peptides and Proteins, Karyopherins, Mediator Complex, Proteins, RNA Interference, RNA, Small Interfering, Transcription, Genetic, Vesicular Transport Proteins, Virus Integration, Virus Internalization, Virus Replication, rab GTP-Binding Proteins

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          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.

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          Author and article information

          Journal
          18187620
          10.1126/science.1152725

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