Identification of host proteins required for HIV infection through a functional genomic screen.
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.
Brass
Abraham L
AL
Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Dykxhoorn
Derek M
DM
Benita
Yair
Y
Yan
Nan
N
Engelman
Alan
A
Xavier
Ramnik J
RJ
Lieberman
Judy
J
Elledge
Stephen J
SJ
D045744:Cell Line, Tumor; D019295:Computational Biology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology; D023281:Genomics; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions; D054298:Human Immunodeficiency Virus Proteins / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D028884:Karyopherins / Q000235:genetics / Q000502:physiology; D056892:Mediator Complex; D011506:Proteins / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D014158:Transcription, Genetic; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000502:physiology; D016662:Virus Integration; D053586:Virus Internalization; D014779:Virus Replication; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000502:physiology
D003598:Cytoskeletal Proteins; D054298:Human Immunodeficiency Virus Proteins; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; C496877:MED28 protein, human; D056892:Mediator Complex; D011506:Proteins; D034741:RNA, Small Interfering; C094135:Rab6 protein; C503307:VPS53 protein, human; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins