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Virology. 2018 Sep;522:199-208. doi: 10.1016/j.virol.2018.07.014. Epub 2018 Jul 20.

Toll-like receptor agonist R848 blocks Zika virus replication by inducing the antiviral protein viperin.

Author information

1
Department of Microbiology, NYU School of Medicine, New York, NY, USA.
2
Department of Microbiology, NYU School of Medicine, New York, NY, USA. Electronic address: Nathaniel.landau@med.nyu.edu.

Abstract

Zika virus (ZIKV) is an emerging pathogen linked to neurological disorders for which there is currently no targeted therapy. To identify host innate immune response proteins that restrict ZIKV replication, we treated monocytes and macrophages with toll-like receptor (TLR) agonists. Of those tested, the TLR7/8 agonist R848 (resiquimod) was the most potent inhibitor of ZIKV replication. RNA-seq analysis identified several genes strongly induced by R848 in monocytes. Testing of several of these for their ability to restrict ZIKV replication identified viperin, an interferon-induced gene active against several viruses. Transduction of microglial CHME3 cells with a viperin lentiviral expression vector rendered them resistant to ZIKV infection, preventing the synthesis of viral RNA and protein. CRISPR/Cas9 knock-out of viperin in macrophages relieved the block to infection, demonstrating that viperin is a major innate immune response protein able to block ZIKV replication. TLR agonists may be useful for the prophylactic or therapeutic treatment for ZIKV.

KEYWORDS:

Monocytes; R848; RNA synthesis; TLR7/8; Viperin; ZIKV restriction

PMID:
30036788
PMCID:
PMC6130814
DOI:
10.1016/j.virol.2018.07.014
[Indexed for MEDLINE]
Free PMC Article

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