title: Inhibition of highly pathogenic avian influenza virus H5N1 replication by the small interfering RNA targeting polymerase A gene.
abstract: RNA interference is a form of post-transcriptional gene silencing mediated by small interfering RNAs (siRNAs), and it provides a powerful new means to specifically inhibit viral infection. In this study, three siRNAs (ps-PA496, ps-PA1116, and ps-PA1473) targeting the polymerase A (PA) gene of highly pathogenic avian influenza virus (HPAIV) H5N1 were designed and evaluated for their abilities to inhibit HPAIV replication. Results in vitro showed that the viral replication in the siRNAs-treated cells was 78-fold lower than that of the control for ps-PA496. Real-time PCR and indirect immunofluorescence assay also showed a significant reduction of the viral RNA level and protein expression. In vivo results showed a significant decrease of lung virus titers and an increase in the survival rate of infected mice pretreated with ps-PA496. These findings suggested that siRNAs targeting PA could efficiently inhibit HPAIV replication and these conserved regions might become potential therapeutic targets against influenza virus infection.
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Cheng-yu
authors.initials: CY
authors.lastname: Wang
authors.forename: Song-tao
authors.initials: ST
authors.lastname: Yang
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.forename: Jia-lin
authors.initials: JL
authors.lastname: Hu
authors.forename: Xian-zhu
authors.initials: XZ
authors.lastname: Xia
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004285:Dogs; D005260:Female; D018390:Gene Targeting; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology* / Q000472:pathogenicity / Q000502:physiology; D007251:Influenza, Human / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics* / Q000627:therapeutic use; D014779:Virus Replication / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D012318:RNA Polymerase I