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High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
10:16

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication

Published on: October 30, 2021

4.2K

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

Bénédicte Vanwalscappel1, Takuya Tada1, Nathaniel R Landau1

  • 1Department of Microbiology, NYU School of Medicine, New York, NY, USA.

Virology
|July 24, 2018
PubMed

Insights

Researchers identified viperin as a key protein that restricts Zika virus (ZIKV) replication. Toll-like receptor (TLR) agonists, like R848, can induce viperin, offering potential therapeutic strategies against ZIKV.

Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Zika virus (ZIKV) is an emerging pathogen associated with neurological disorders.
  • No specific antiviral therapy currently exists for ZIKV infections.

Purpose of the Study:

  • To identify host innate immune proteins that restrict ZIKV replication.
  • To evaluate the potential of toll-like receptor (TLR) agonists as therapeutic agents against ZIKV.

Main Methods:

  • Monocytes and macrophages were treated with TLR agonists, including R848 (resiquimod).
  • RNA-sequencing (RNA-seq) was performed to identify R848-induced genes.
  • Viperin's antiviral activity was assessed in microglial cells and macrophages using lentiviral vectors and CRISPR/Cas9 gene editing.

Main Results:

  • The TLR7/8 agonist R848 significantly inhibited ZIKV replication.
  • Viperin was identified as a major R848-induced gene that restricts ZIKV.
  • Overexpression of viperin conferred resistance to ZIKV infection, while its knockout abolished this resistance.

Conclusions:

  • Viperin is a crucial innate immune protein that effectively blocks ZIKV replication.
  • TLR agonists, by inducing viperin, show promise for prophylactic or therapeutic interventions against ZIKV.
Keywords:
MonocytesR848RNA synthesisTLR7/8ViperinZIKV restriction

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