4.7 Article

Inhibition of Japanese encephalitis virus replication by peptide nucleic acids targeting cis-acting elements on the plus- and minus-strands of viral RNA

期刊

ANTIVIRAL RESEARCH
卷 82, 期 3, 页码 122-133

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2009.02.187

关键词

JEV; Peptide nucleic acids (PNAs); Antisense; RdRp; cis-Acting element

资金

  1. Basic Research Program of the Korea Science and Engineering Foundation [RO1-2004-000-103820]
  2. Korea Research Foundation [KRF-2004-C00148]
  3. Korean Government
  4. Korean Ministry of Education, Science, and Technology

向作者/读者索取更多资源

Japanese encephalitis virus (JEV) is a major cause of acute viral encephalitis in humans. The single-stranded, plus-sense viral genome, which is used for translation and minus-strand RNA synthesis, and its complementary minus-strand viral RNA contain various sequences and RNA secondary structures conserved in flaviviruses, providing potential targets for antisense agents. Here, we investigated the antiviral effects of peptide nucleic acids (PNAs) targeting cis-acting signals at the 5'-untranslated region (UTR), 3'-UTR, and genome cyclization motifs on the plus-strand RNA, as well as the 95-nucleotide 3'-end of the minus-strand RNA, which serves as a template for plus-strand RNA synthesis by the viral RNA-dependent RNA polymerase (RdRp). Among the tested cell-penetrating peptide (CPP)-PNA conjugates, a 17-mer PNA conjugate targeting the top of the 3'-UTR loop structure was most effective in suppressing virus proliferation. In vitro RdRp assays and electrophoretic mobility shift assays using a functional recombinant JEV RdRp showed that the 3'-terminal region-targeting PNAs could inhibit RNA synthesis by competing with viral RdRp for binding to a selected cis-acting element at the 3'-end of plus- and minus-strand viral RNAs. Collectively, our results suggest that CPP-PNA conjugates can suppress JEV proliferation by blocking RNA-protein or RNA-RNA interactions essential for productive viral infection. (C) 2009 Elsevier B.V. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据