title: RNA interference targeted to the conserved dimerization initiation site (DIS) of HIV-1 restricts virus escape mutation.
abstract: Short hairpin RNAs (shRNA) targeting viral or cellular genes can effectively inhibit human immunodeficiency virus type 1 (HIV-1) replication. This inhibition, however, may induce mutations in the targeted gene, leading to rapid escape from the shRNA-induced inhibition. We generated a lymphoid cell line that stably expressed a 19-bp shRNA targeting a well-conserved dimerization initiation site (DIS) of HIV-1, which strongly inhibited viral replication, thereby delaying virus escape. Furthermore, treatment of HIV-1 infection with DIS- and vif-shRNA combination therapy resulted in superior anti-viral responses compared to vif-shRNA monotherapy. Continuous challenge with HIV-1, however, generated virus mutants that could overcome the RNA interference restriction. Such anti-genes may be promising tools for HIV-1 gene therapy for HIV/acquired immunodeficiency syndrome.
authors: Department of Life and Environmental Science, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino-shi, Chiba 275-0016, Japan.
authors: Ryuichi
authors: R
authors: Sugiyama
authors: Yuichiro
authors: Y
authors: Habu
authors: Aki
authors: A
authors: Ohnari
authors: Naoko
authors: N
authors: Miyano-Kurosaki
authors: Hiroshi
authors: H
authors: Takaku
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D002460:Cell Line; D017124:Conserved Sequence / Q000235:genetics*; D019281:Dimerization; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009690:Nucleic Acid Conformation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D034741:RNA, Small Interfering