Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication
| العنوان: | Small Interfering RNA Targeting M2 Gene Induces Effective and Long Term Inhibition of Influenza A Virus Replication |
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| المؤلفون: | Bo-Jian Zheng, Kwok-Yung Yuen, Dong-Yan Jin, Jian-Dong Huang, Guangyu Zhao, Hongyan Sui |
| المصدر: | PLoS ONE PLoS ONE, Vol 4, Iss 5, p e5671 (2009) |
| بيانات النشر: | Public Library of Science (PLoS), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Gene Expression Regulation, Viral, RNA, Messenger - genetics - metabolism, Small interfering RNA, Time Factors, Molecular Sequence Data, Influenza A Virus, H1N1 Subtype - genetics - physiology, lcsh:Medicine, Biology, medicine.disease_cause, Virus Replication, Viral Matrix Proteins - genetics, Virus, Virology/Emerging Viral Diseases, Viral vector, Cell Line, Small hairpin RNA, Viral Matrix Proteins, Influenza A Virus, H1N1 Subtype, Dogs, Nucleocapsid Proteins - genetics - metabolism, Orthomyxoviridae Infections, Mutation - genetics, RNA interference, Virology, medicine, Influenza A virus, Animals, RNA, Messenger, RNA, Small Interfering, Serial Passage, lcsh:Science, Influenza A Virus, H5N1 Subtype - genetics - physiology, Virology/Antivirals, including Modes of Action and Resistance, Multidisciplinary, Influenza A Virus, H5N1 Subtype, Base Sequence, Virus Assembly, lcsh:R, RNA, Small Interfering - genetics, Nucleocapsid Proteins, Virus Replication - physiology, Influenza A virus subtype H5N1, Viral replication, Mutation, lcsh:Q, Orthomyxoviridae Infections - virology, Research Article |
| الوصف: | RNA 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. published_or_final_version |
| تدمد: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0005671 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d3845f4482fe7251e91abb9abfa3609b |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d3845f4482fe7251e91abb9abfa3609b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0005671 |