Abstract |
Small interfering RNAs (siRNAs) targeting rabies virus (RV) glycoprotein (G) and nucleoprotein (N) genes were evaluated as antiviral agents against rabies virus in vitro in BHK-21 cells. To select effective siRNAs targeting RV-G, a plasmid-based transient co-transfection approach was used. In this, siRNAs were expressed as short hairpin RNAs (shRNAs), and their ability to inhibit RV-G gene expression was evaluated in cells transfected with a plasmid expressing RV-G. The nine different siRNAs designed to target RV-G exhibited varying degrees of knockdown of RV-G gene expression. One siRNA (si-G7) with considerable effect in knockdown of RV-G expression also demonstrated significant inhibition of RV multiplication in BHK-21 cells after in vitro challenge with the RV Pasteur virus-11 (PV-11) strain. A decrease in the number of fluorescent foci in siRNA-treated cells and a reduction (86.8 %) in the release of RV into infected cell culture supernatant indicated the anti- rabies potential of siRNA. Similarly, treatment with one siRNA targeting RV-N resulted in a decrease in the number of fluorescent foci and a reduction (85.9 %) in the release of RV. As a dual gene silencing approach where siRNAs targeting RV-G and RV-N genes were expressed from single construct, the anti-rabies-virus effect was observed as an 87.4 % reduction in the release of RV. These results demonstrate that siRNAs targeting RV-G and N, both in single and dual form, have potential as antiviral agent against rabies.
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Authors | Chetan D Meshram, Niraj K Singh, Arvind A Sonwane, Sachin S Pawar, B P Mishra, V K Chaturvedi, Mohini Saini, R P Singh, Praveen K Gupta |
Journal | Archives of virology
(Arch Virol)
Vol. 158
Issue 11
Pg. 2323-32
(Nov 2013)
ISSN: 1432-8798 [Electronic] Austria |
PMID | 23754741
(Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Viral
- Antiviral Agents
- Glycoproteins
- Nucleocapsid Proteins
- RNA, Small Interfering
- Viral Envelope Proteins
- glycoprotein G, Rabies virus
- nucleocapsid protein, Rabies virus
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Topics |
- Animals
- Antigens, Viral
(genetics, metabolism)
- Antiviral Agents
(pharmacology)
- Cell Line
- Cricetinae
- Gene Silencing
- Glycoproteins
(genetics, metabolism)
- HEK293 Cells
- Humans
- Nucleocapsid Proteins
(genetics, metabolism)
- RNA, Small Interfering
(genetics, metabolism, pharmacology)
- Rabies
(drug therapy, virology)
- Rabies virus
(drug effects, genetics, physiology)
- Viral Envelope Proteins
(genetics, metabolism)
- Virus Replication
(drug effects)
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