Significant inhibition of Tembusu virus envelope and NS5 gene using an adenovirus-mediated short hairpin RNA delivery system
| Autor: | Youxiang Diao, Yi Tang, Chen Hao, Hongzhi Wang, Lei Wei, Qiang Feng, Liling Zhuo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Gene Expression Regulation Viral viruses 030106 microbiology Down-Regulation Viral Nonstructural Proteins Virus Replication Microbiology Viral vector law.invention Adenoviridae Flavivirus Infections Small hairpin RNA 03 medical and health sciences RNA interference law Chlorocebus aethiops Genetics Animals Humans Gene Silencing RNA Small Interfering Molecular Biology Gene Vero Cells Ecology Evolution Behavior and Systematics biology Flavivirus RNA Viral Load biology.organism_classification Virology 030104 developmental biology Infectious Diseases HEK293 Cells Vero cell Recombinant DNA |
| Zdroj: | Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 54 |
| ISSN: | 1567-7257 |
| Popis: | Tembusu virus (TMUV) is a mosquito-borne flavivirus, which was first isolated in the tropics during the 1970s. Recently, a disease characterized by ovarian haemorrhage and neurological symptoms was observed in ducks in China, which threatens poultry production. However, there is no suitable vaccination strategy or effective antiviral drugs to combat TMUV infections. Consequently, there is an urgent need to develop a new anti-TMUV therapy. In this study, we report an efficient short hairpin RNA (shRNA) delivery strategy for the inhibition of TMUV production using an adenovirus vector system. Using specifically designed shRNAs based on the E and NS5 protein genes of TMUV, the vector-expressed viral genes, TMUV RNA replication and infectious virus production were downregulated at different levels in Vero cells, where the shRNA (NS52) was highly effective in inhibiting TMUV. Using the human adenovirus type 5 shRNA delivery system, the recombinant adenovirus (rAd-NS52) inhibited TMUV multiplication with high efficiency. Furthermore, the significant dose-dependent inhibition of viral RNA copies induced by rAd-NS52 was found in TMUV-infected cells, which could last for at least 96h post infection. Our results indicated that the adenovirus-mediated delivery of shRNAs could play an active role in future TMUV antiviral therapeutics. |
| Databáze: | OpenAIRE |
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