Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies

Frederic D. Bushman(University of Pennsylvania), Nirav Malani(University of Pennsylvania), Jason D. Fernandes(University of California, San Francisco), Iván D’Orso(University of California, San Francisco), Gerard Cagney(Houston Advanced Research Center), Tracy L. Diamond(United States Military Academy), Honglin Zhou(United States Military Academy), Daria J. Hazuda(United States Military Academy), Amy S. Espeseth(United States Military Academy), Renate König(Sanford Burnham Prebys Medical Discovery Institute), Sourav Bandyopadhyay(University of California, San Diego), Trey Ideker(University of California, San Diego), Stephen P. Goff(Howard Hughes Medical Institute), Nevan J. Krogan(University of California, San Francisco), Alan D. Frankel(Houston Advanced Research Center), John A. T. Young(Salk Institute for Biological Studies), Sumit K. Chanda(Sanford Burnham Prebys Medical Discovery Institute)
PLoS Pathogens
May 28, 2009
Cited by 442Open Access
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Abstract

We have analyzed host cell genes linked to HIV replication that were identified in nine genome-wide studies, including three independent siRNA screens. Overlaps among the siRNA screens were very modest (<7% for any pairwise combination), and similarly, only modest overlaps were seen in pairwise comparisons with other types of genome-wide studies. Combining all genes from the genome-wide studies together with genes reported in the literature to affect HIV yields 2,410 protein-coding genes, or fully 9.5% of all human genes (though of course some of these are false positive calls). Here we report an "encyclopedia" of all overlaps between studies (available at http://www.hostpathogen.org), which yielded a more extensively corroborated set of host factors assisting HIV replication. We used these genes to calculate refined networks that specify cellular subsystems recruited by HIV to assist in replication, and present additional analysis specifying host cell genes that are attractive as potential therapeutic targets.


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