Publication Date:
2008-01-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brass, Abraham L -- Dykxhoorn, Derek M -- Benita, Yair -- Yan, Nan -- Engelman, Alan -- Xavier, Ramnik J -- Lieberman, Judy -- Elledge, Stephen J -- AI052014/AI/NIAID NIH HHS/ -- AI062773/AI/NIAID NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- P30 DK040561/DK/NIDDK NIH HHS/ -- P30 DK040561-13/DK/NIDDK NIH HHS/ -- U19-AI056900/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Feb 15;319(5865):921-6. doi: 10.1126/science.1152725. Epub 2008 Jan 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18187620" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line, Tumor
;
Computational Biology
;
Cytoskeletal Proteins/genetics/physiology
;
Genomics
;
HIV Infections/genetics/metabolism/*virology
;
HIV-1/genetics/pathogenicity/*physiology
;
Host-Pathogen Interactions
;
Human Immunodeficiency Virus Proteins/physiology
;
Humans
;
Intracellular Signaling Peptides and Proteins/genetics/physiology
;
Karyopherins/genetics/physiology
;
Mediator Complex
;
Proteins/*physiology
;
RNA Interference
;
RNA, Small Interfering
;
Transcription, Genetic
;
Vesicular Transport Proteins/genetics/physiology
;
Virus Integration
;
Virus Internalization
;
Virus Replication
;
rab GTP-Binding Proteins/genetics/physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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