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Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.3K

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Related Experiment Video

Updated: Oct 12, 2025

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
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A CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry.

Anh Phuong Luu1, Zhenlan Yao1, Sangeetha Ramachandran1

  • 1Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.

Viruses
|November 27, 2021
PubMed
Summary

Researchers identified RhoV as a key protein promoting Zika virus (ZIKV) infection by aiding viral entry. This finding highlights new therapeutic targets for ZIKV, a virus lacking approved treatments.

Keywords:
CRISPR activationRho GTPasesRhoVWWTR1Zika virusproviral factors

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Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Zika virus (ZIKV) is a re-emerging flavivirus causing epidemics with severe neurologic consequences, particularly in newborns.
  • Current therapeutic and vaccine options for ZIKV infection are limited, necessitating the identification of host factors for targeted interventions.

Purpose of the Study:

  • To identify host cellular pathways and genes essential for ZIKV replication using a CRISPR-Cas9 activation screen.
  • To uncover potential therapeutic targets for ZIKV infection by understanding host-pathogen interactions.

Main Methods:

  • Utilized a CRISPR-Cas9 gene activation system in interferon-deficient human fibroblasts to upregulate all coding genes.
  • Screened for genes that enhance ZIKV infection and validated the role of identified proviral factors, including RhoV, RhoB, and Pak1.
  • Investigated the mechanism of RhoV in ZIKV infection, focusing on its GTPase cycle and role in viral entry.

Main Results:

  • Identified Ras homolog family member V (RhoV) and WW domain-containing transcription regulator 1 (WWTR1) as proviral factors crucial for early ZIKV infection.
  • Validated RhoV's role in promoting ZIKV infection and virion production, demonstrating its function at the viral entry stage.
  • Discovered that RhoV's proviral activity is dependent on its GTPase cycle and identified RhoB and Pak1 as additional proviral factors.

Conclusions:

  • RhoV is a significant proviral factor that facilitates ZIKV infection, particularly at the entry step, offering a potential therapeutic target.
  • CRISPR activation screens are effective for discovering novel host-pathogen interactions and identifying therapeutic targets for viral diseases like ZIKV.