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

Ji Seung Yoo, Chan Mi Kim, Jung Hee Kim, Jee Yon Kim, Jong-Won Oh

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)122-133
Number of pages12
JournalAntiviral Research
Volume82
Issue number3
DOIs
Publication statusPublished - 2009 Jun 1

Fingerprint

Japanese Encephalitis Virus
Peptide Nucleic Acids
Viral RNA
RNA
RNA Replicase
5' Untranslated Regions
Cell-Penetrating Peptides
3' Untranslated Regions
Viral Encephalitis
Flavivirus
Viral Genome
Electrophoretic Mobility Shift Assay
Virus Diseases
Cyclization
Antiviral Agents
Nucleotides
Genome

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

Cite this

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title = "Inhibition of Japanese encephalitis virus replication by peptide nucleic acids targeting cis-acting elements on the plus- and minus-strands of viral RNA",
abstract = "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.",
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Inhibition of Japanese encephalitis virus replication by peptide nucleic acids targeting cis-acting elements on the plus- and minus-strands of viral RNA. / Yoo, Ji Seung; Kim, Chan Mi; Kim, Jung Hee; Kim, Jee Yon; Oh, Jong-Won.

In: Antiviral Research, Vol. 82, No. 3, 01.06.2009, p. 122-133.

Research output: Contribution to journalArticle

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