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Article: Small interfering RNA targeting M2 gene induces effective and long term inhibition of influenza A virus replication

TitleSmall interfering RNA targeting M2 gene induces effective and long term inhibition of influenza A virus replication
Authors
Issue Date2009
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2009, v. 4 n. 5 How to Cite?
AbstractRNA interference (RNAi) provides a powerful new means to inhibit viral infection specifically. However, the selection of siRNA-resistant viruses is a major concern in the use of RNAi as antiviral therapeutics. In this study, we conducted a lentiviral vector with a H1-short hairpin RNA (shRNA) expression cassette to deliver small interfering RNAs (siRNAs) into mammalian cells. Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed. The results showed that a siRNA targeting influenza M2 gene (siM2) potently inhibited viral replication. The siM2 was not only effective for H1N1 virus but also for highly pathogenic avian influenza virus H5N1. In addition to its M2 inhibition, the siM2 also inhibited NP mRNA accumulation and protein expression. A long term inhibition effect of the siM2 was demonstrated and the emergence of siRNA-resistant mutants in influenza quasispecies was not observed. Taken together, our study suggested that M2 gene might be an optimal RNAi target for antiviral therapy. These findings provide useful information for the development of RNAi-based prophylaxis and therapy for human influenza virus infection. © 2009 Sui et al.
Persistent Identifierhttp://hdl.handle.net/10722/58277
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSui, HYen_HK
dc.contributor.authorZhao, GYen_HK
dc.contributor.authorHuang, JDen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorYuen, KYen_HK
dc.contributor.authorZheng, BJen_HK
dc.date.accessioned2010-05-31T03:27:17Z-
dc.date.available2010-05-31T03:27:17Z-
dc.date.issued2009en_HK
dc.identifier.citationPlos One, 2009, v. 4 n. 5en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58277-
dc.description.abstractRNA interference (RNAi) provides a powerful new means to inhibit viral infection specifically. However, the selection of siRNA-resistant viruses is a major concern in the use of RNAi as antiviral therapeutics. In this study, we conducted a lentiviral vector with a H1-short hairpin RNA (shRNA) expression cassette to deliver small interfering RNAs (siRNAs) into mammalian cells. Using this vector that also expresses enhanced green fluorescence protein (EGFP) as surrogate marker, stable shRNA-expressing cell lines were successfully established and the inhibition efficiencies of rationally designed siRNAs targeting to conserved regions of influenza A virus genome were assessed. The results showed that a siRNA targeting influenza M2 gene (siM2) potently inhibited viral replication. The siM2 was not only effective for H1N1 virus but also for highly pathogenic avian influenza virus H5N1. In addition to its M2 inhibition, the siM2 also inhibited NP mRNA accumulation and protein expression. A long term inhibition effect of the siM2 was demonstrated and the emergence of siRNA-resistant mutants in influenza quasispecies was not observed. Taken together, our study suggested that M2 gene might be an optimal RNAi target for antiviral therapy. These findings provide useful information for the development of RNAi-based prophylaxis and therapy for human influenza virus infection. © 2009 Sui et al.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAnimalsen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshDogsen_HK
dc.subject.meshGene Expression Regulation, Viralen_HK
dc.subject.meshInfluenza A Virus, H1N1 Subtype - genetics - physiologyen_HK
dc.subject.meshInfluenza A Virus, H5N1 Subtype - genetics - physiologyen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshMutation - geneticsen_HK
dc.subject.meshNucleocapsid Proteins - genetics - metabolismen_HK
dc.subject.meshOrthomyxoviridae Infections - virologyen_HK
dc.subject.meshRNA, Messenger - genetics - metabolismen_HK
dc.subject.meshRNA, Small Interfering - geneticsen_HK
dc.subject.meshSerial Passageen_HK
dc.subject.meshTime Factorsen_HK
dc.subject.meshViral Matrix Proteins - geneticsen_HK
dc.subject.meshVirus Assemblyen_HK
dc.subject.meshVirus Replication - physiologyen_HK
dc.titleSmall interfering RNA targeting M2 gene induces effective and long term inhibition of influenza A virus replicationen_HK
dc.typeArticleen_HK
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0005671en_HK
dc.identifier.pmid19479060-
dc.identifier.scopuseid_2-s2.0-66249096334en_HK
dc.identifier.hkuros156489en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-66249096334&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume4en_HK
dc.identifier.issue5en_HK
dc.identifier.isiWOS:000266331200008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridSui, HY=23971615600en_HK
dc.identifier.scopusauthoridZhao, GY=8684553000en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.citeulike4681296-

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