title: Long-term inhibition of HIV-1 replication with RNA interference against cellular co-factors.
abstract: In this study we tested whether HIV-1 replication could be inhibited by stable RNAi-mediated knockdown of cellular co-factors. Cell lines capable of expressing shRNAs against 30 candidate co-factors implicated at different steps of the viral replication cycle were generated and analyzed for effects on cell viability and inhibition of HIV-1 replication. For half of these candidate co-factors we obtained knockdown cell lines that are less susceptible to virus replication. For three co-factors (ALIX, ATG16 and TRBP) the cell lines were resistant to HIV-1 replication for up to 2 months. With these cells we could test the hypothesis that HIV-1 is not able to escape from RNAi-mediated suppression of cellular co-factors, which was indeed not detected.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Julia J M
authors.initials: JJ
authors.lastname: Eekels
authors.forename: Dirk
authors.initials: D
authors.lastname: Geerts
authors.forename: Rienk E
authors.initials: RE
authors.lastname: Jeeninga
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
mesh_terms: D000071183:Autophagy-Related Proteins; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D002460:Cell Line; D002470:Cell Survival; D056827:Endosomal Sorting Complexes Required for Transport / Q000037:antagonists & inhibitors; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors; D013997:Time Factors; D014779:Virus Replication; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D000071183:Autophagy-Related Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000099253:Trans-Activation Responsive RNA-Binding Protein; C518959:ATG16L1 protein, human; C117020:PDCD6IP protein, human