Attenuation of dengue virus infection by adeno-associated virus-mediated siRNA delivery |
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| Authors: | Weidong Zhang Rajeswari Singam Gary Hellermann Xiaoyuan Kong Homero San Juan Richard F Lockey Shuen-Ju Wu Kevin Porter Shyam S Mohapatra |
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| Institution: | Division of Allergy and Immunology-JMC Airway Disease Research Center, Department of Internal Medicine, University of South Florida; VA Hospital Tampa, FL, USA. smohapat@hsc.usf.edu |
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| Abstract: | BACKGROUND: The need for safe and effective treatment of dengue virus (DEN), a class A agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. An effective vaccine for DEN is not yet available. In this study the possibility of attenuating DEN infection using adeno-associated virus (AAV)-encoded short interfering RNAs (siRNA) was examined in Vero cells and human dendritic cells (DCs). METHODS: A cassette encoding siRNA targeted to a 3' untranslated sequence common to all DEN serotypes was designed and tested for its ability to attenuate DEN infection by use of AAV delivery. RESULTS: Vero cells or DCs infected with AAV-siRNA showed a significant, dose-dependent reduction in DEN infection. Treatment of DCs with AAV-siRNA also decreased the DEN-induced apoptosis of DCs and did not induce significant inflammation. CONCLUSION: These results demonstrate that AAV-mediated siRNA delivery is capable of reducing DEN infection in cells and may be useful in decreasing DEN replication in humans. |
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