@article{APS9456,
author = {Yuan-yuan LIU and Liang-jun CHEN and Yan ZHONG and Meng-xin SHEN and Nian MA and Bing-yu LIU and Fan LUO and Wei HOU and Zhan-qiu YANG and Hai-rong XIONG},
title = {Specific interference shRNA-expressing plasmids inhibit Hantaan virus infection in vitro and in vivo },
journal = {Acta Pharmacologica Sinica},
volume = {37},
number = {4},
year = {2017},
keywords = {},
abstract = {Aim: To investigate the antiviral effects of vectors expressing specific short hairpin RNAs (shRNAs) against Hantaan virus (HTNV) infection in vitro and in vivo.
Methods: Based on the effects of 4 shRNAs targeting different regions of HTNV genomic RNA on viral replication, the most effective RNA interference fragments of the S and M genes were constructed in pSilencer-3.0-H1 vectors, and designated pSilencer-S and pSilencer-M, respectively. The antiviral effect of pSilencer-S/M against HTNV was evaluated in both HTNV-infected Vero-E6 cells and mice.
Results: In HTNV-infected Vero-E6 cells, pSilencer-S and pSilencer-M targeted the viral nucleocapsid proteins and envelope glycoproteins, respectively, as revealed in the immunofluorescence assay. Transfection with pSilencer-S or pSilencer-M (1, 2, and 4 μg) markedly inhibited the viral antigen expression in dose- and time-dependent manners. Transfection with either plasmid (2 μg) significantly decreased HTNV-RNA level at 3 day postinfectin (dpi) and the progeny virus titer at 5 dpi. In mice infected with lethal doses of HTNV, intraperitoneal injection of pSilencer-S or pSilencer-M (30 μg) considerably increased the survival rates and mean time to death, and significantly reduced the mean virus yields and viral RNA level, and alleviated virus-induced pathological lesions in lungs, brains and kidneys.
Conclusion: Plasmid-based shRNAs potently inhibit HTNV replication in vitro and in vivo. Our results provide a basis for development of shRNA as therapeutics for HTNV infections in humans.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9456}
}