Viruses, Vol. 13, Pages 2113: A CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry

Viruses, Vol. 13, Pages 2113: A CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry Viruses doi: 10.3390/v13112113 Authors: Anh Phuong Luu Zhenlan Yao Sangeetha Ramachandran Stephanie A. Azzopardi Linde A. Miles William M. Schneider H.-Heinrich Hoffmann Leonia Bozzacco Gustavo Garcia Danyang Gong Robert Damoiseaux Hengli Tang Kouki Morizono Charles M. Rudin Ren Sun Vaithilingaraja Arumugaswami John T. Poirier Margaret R. MacDonald Charles M. Rice Melody M. H. Li 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...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research