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

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-? (interferon ?) RANTES (regulated on activation, normal T cell expressed and secreted), MIP-1? (macrophage inflammatory protein-1?), TNF-? (tumor necrosis factor-?) and IL1-? (interleukin 1-?) 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.

SUBMITTER: Popik W 

PROVIDER: S-EPMC6503319 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature