Knockdown of Cellular RNA Helicase DDX3 by Short Hairpin RNAs Suppresses HIV-1 Viral Replication Without Inducing Apoptosis
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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.
KeywordsHIV-1 RNA helicase DDX3 RNAi Short hairpin RNA RNA nuclear export
We thank Dr. Kuan-The Jeang for providing DDX3-HA plasmid, Dr. John Rossi for shRNA Rev, and Dr Ke Zhuang for Ghost (CD4/CCR5) cells. This study was supported by China “863” programme (grant 2006AA02Z123), China “973” programme (grant 2006CB504305), and the MOE “111” project #B06018.
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