A CRISPR activation screen identifies an atypical Rho GTPase that enhances zika viral entry Journal Article

Authors: Luu, A. P.; Yao, Z.; Ramachandran, S.; Azzopardi, S. A.; Miles, L. A.; Schneider, W. M.; Hoffmann, H. H.; Bozzacco, L.; Garcia, G. Jr; Gong, D.; Damoiseaux, R.; Tang, H.; Morizono, K.; Rudin, C. M.; Sun, R.; Arumugaswami, V.; Poirier, J. T.; Macdonald, M. R.; Rice, C. M.; Li, M. M. H.
Article Title: A CRISPR activation screen identifies an atypical Rho GTPase that enhances zika viral entry
Abstract: Zika virus (ZIKV) is a re-emerging flavivirus that has caused large-scale epidemics. Infection during pregnancy can lead to neurologic developmental abnormalities in children. There is no approved vaccine or therapy for ZIKV. To uncover cellular pathways required for ZIKV that can be therapeutically targeted, we transcriptionally upregulated all known human coding genes with an engineered CRISPR–Cas9 activation complex in human fibroblasts deficient in interferon (IFN) signaling. We identified Ras homolog family member V (RhoV) and WW domain-containing transcription regulator 1 (WWTR1) as proviral factors, and found them to play important roles during early ZIKV infection in A549 cells. We then focused on RhoV, a Rho GTPase with atypical terminal sequences and membrane association, and validated its proviral effects on ZIKV infection and virion production in SNB-19 cells. We found that RhoV promotes infection of some flaviviruses and acts at the step of viral entry. Furthermore, RhoV proviral effects depend on the complete GTPase cycle. By depleting Rho GTPases and related proteins, we identified RhoB and Pak1 as additional proviral factors. Taken together, these results highlight the positive role of RhoV in ZIKV infection and confirm CRISPR activation as a relevant method to identify novel host–pathogen interactions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: rho gtpases; wwtr1; zika virus; crispr activation; proviral factors; rhov
Journal Title: Viruses
Volume: 13
Issue: 11
ISSN: 1999-4915
Publisher: MDPI  
Date Published: 2021-11-01
Start Page: 2113
Language: English
DOI: 10.3390/v13112113
PROVIDER: scopus
PMCID: PMC8623001
PUBMED: 34834920
Notes: Article -- Export Date: 1 December 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Charles Rudin
    345 Rudin
  2. Linde Anne Miles
    16 Miles