Phosphorodiamidate morpholino targeting the 5′ untranslated region of the ZIKV RNA inhibits virus replication

Waldemar Popik, Atanu Khatua, James Hildreth, Benjamin Lee, Donald J. Alcendor

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Zika virus (ZIKV) infection has been associated with microcephaly in infants. Currently there is no treatment or vaccine. Here we explore the use of a morpholino oligonucleotide targeted to the 5′ untranslated region (5′-UTR) of the ZIKV RNA to prevent ZIKV replication. Methods: Morpholino DWK-1 inhibition of ZIKV replication in human glomerular podocytes was examined by qRT-PCR, reduction in ZIKV genome copy number, western blot analysis, immunofluorescence and proinflammatory cytokine gene expression. Results: Podocytes pretreated with DWK-1 showed reduced levels of both viral mRNA and ZIKV E protein expression compared to controls. We observed suppression in proinflammatory gene expression for IFN-β (interferon β) RANTES (regulated on activation, normal T cell expressed and secreted), MIP-1α (macrophage inflammatory protein-1α), TNF-α (tumor necrosis factor-α) and IL1-α (interleukin 1-α) in ZIKV-infected podocytes pretreated with DWK-1. Conclusions: Morpholino DWK-1 targeting the ZIKV 5′-UTR effectively inhibits ZIKV replication and suppresses ZIKV-induced proinflammatory gene expression.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalVirology
Volume519
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

Keywords

  • Antiviral
  • Inflammation
  • Morpholino
  • Podocyte
  • Therapy
  • Zika virus

ASJC Scopus subject areas

  • Virology

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