Utilizing liver-specific microRNA-122 to modulate replication of dengue virus replicon.
microRNAs (miRNAs) are endogenous non-coding RNAs that spatiotemporally modulate mRNAs in a post-transcriptional manner. The engineering of viruses by insertion of a tissue-specific miRNA recognition element (MRE) into viral mRNA can restrict viral tissue tropism. In this study we employed dengue virus (DEN) replicons to investigate whether miRNAs are able to suppress flavivirus replication through the targeting of non-polyadenylated viral mRNA. Because liver infection by DEN may contribute to the virus pathogenesis, we inserted an MRE of hepatic-specific microRNA-122 (miR-122) into its 3'-untranslated region (3'-UTR) to test the feasibility of creating a liver-restricted DEN replicon. Our results demonstrate that incorporation of the miR-122-MRE confers upon the DEN replicon an inhibitory susceptibility to miR-122 targeting, suggesting that DEN can be engineered to exert the desired replication restriction effect to avoid infection of vital tissues/organs. This approach provides an additional layer of biosafety and thus has great potential for use in the rational development of safer flavivirus vaccines.
Lee
Tai-Chi
TC
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Lin
Yi-Ling
YL
Liao
Jia-Teh
JT
Su
Chih-Mao
CM
Lin
Chang-Chi
CC
Lin
Wen-Po
WP
Liao
Ching-Len
CL
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D003716:Dengue Virus / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D008099:Liver / Q000821:virology*; D035683:MicroRNAs / Q000235:genetics*; D012093:Replicon; D014779:Virus Replication
D020413:3' Untranslated Regions; C531907:MIRN122 microRNA, human; D035683:MicroRNAs