title: Knockdown of cellular RNA helicase DDX3 by short hairpin RNAs suppresses HIV-1 viral replication without inducing apoptosis.
abstract: The targeting of a cellular co-factor, rather than the HIV-1-specific RNAs, by small interfering RNAs holds promise as the rapid mutational ability of the HIV-1 genome may obviate the potential clinical use of RNAi against this virus. The DEAD-box RNA helicase DDX3 is an essential Rev co-factor in the CRM1-Rev-RRE complex that promotes the export of unspliced and single-spliced HIV-1 RNAs from the nucleus to cytoplasm. In this report, human DDX3 was targeted by specific short hairpin RNAs, and the down-regulation of cell's endogenous DDX3 suppressed the nuclear export of unspliced HIV-1 RNAs but did not affect the cell viability. We further showed that the knockdown of cellular DDX3 could effectively inhibit the replication of HIV-1. Therefore, the current results suggest that the RNA helicase DDX3 may become a potential target by RNAi for future genetic therapy of HIV/AIDS.
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Musarat
authors.initials: M
authors.lastname: Ishaq
authors.forename: Jiajie
authors.initials: J
authors.lastname: Hu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Fu
authors.forename: Yalin
authors.initials: Y
authors.lastname: Yang
authors.forename: Qingzhen
authors.initials: Q
authors.lastname: Liu
authors.forename: Deyin
authors.initials: D
authors.lastname: Guo
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005434:Flow Cytometry; D020868:Gene Silencing; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D012313:RNA / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000502:physiology*
chemical_list: D012313:RNA; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases