Inhibition of highly pathogenic avian influenza virus H5N1 replication by the small interfering RNA targeting polymerase A gene

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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-12, Vol.390 (3), p.421-426
Main Authors: Zhang, Wei, Wang, Cheng-yu, Yang, Song-tao, Qin, Chuan, Hu, Jia-lin, Xia, Xian-zhu
Format: Article
Language:English
Subjects:
Animals
Avian influenza virus
Base Sequence
Cell Line
Dogs
Female
Gene Targeting
Humans
Influenza A Virus, H5N1 Subtype - enzymology
Influenza A Virus, H5N1 Subtype - pathogenicity
Influenza A Virus, H5N1 Subtype - physiology
Influenza virus
Influenza, Human - therapy
Mice
Mice, Inbred BALB C
RNA Polymerase I - antagonists & inhibitors
RNA Polymerase I - genetics
RNA, Small Interfering - genetics
RNA, Small Interfering - therapeutic use
Small interfering RNAs
Virus Replication - genetics
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.09.039