Human H1 promoter expressed short hairpin RNAs (shRNAs) suppress avian influenza virus replication in chicken CH-SAH and canine MDCK cells
| Autor: | Serguei P. Golovan, Arusyak Abrahamyan, Éva Nagy |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Orthomyxoviridae
Chick Embryo Biology Kidney Virus Replication medicine.disease_cause Virus Cell Line Small hairpin RNA Dogs Influenza A Virus H1N1 Subtype Interferon RNA interference Cell Line Tumor Virology Influenza A virus medicine Animals Humans Gene silencing RNA Small Interfering Promoter Regions Genetic Pharmacology RNA Polymerase III Fibroblasts biology.organism_classification Molecular biology Viral replication RNA Viral RNA Interference medicine.drug |
| Zdroj: | Antiviral Research. 84:159-167 |
| ISSN: | 0166-3542 |
| DOI: | 10.1016/j.antiviral.2009.08.009 |
| Popis: | Influenza A virus represents a significant health and economic threat to both humans and animals worldwide. The polymerase III human H1 promoter was used to express nine short hairpin RNAs (shRNAs) targeting nucleocapsid protein (NP) or the acidic component of polymerase complex (PA) genes of avian influenza virus. Tested shRNAs led to a decrease of up to 400 fold in infective titre and up to 80% in the level of viral NP and PA mRNAs in chicken CH-SAH cells (p < 0.05). In mammalian MDCK cells a decrease of up to 10 6 -fold in infective titre, and up to 90% in the level of viral mRNAs (p < 0.05) was detected. While RNAi silencing played a major role in viral inhibition, transfection of any plasmid induced an antiviral interferon response in MDCK cells. In CH-SAH cells, no induction of IFN response was observed by constructs, and the IFN response was suppressed by influenza virus infection. Simultaneous induction of RNAi and IFN responses in CH-SAH cells resulted in 18,500-fold decrease in infective titre (p < 0.05). We also identified novel efficient and conserved RNAi target site in the NP gene which can be used in antiviral cocktails of shRNAs to block the escape of influenza virus. |
| Databáze: | OpenAIRE |
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