A CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry.

TitleA CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry.
Publication TypeJournal Article
Year of Publication2021
AuthorsLuu APhuong, Yao Z, Ramachandran S, Azzopardi SA, Miles LA, Schneider WM, Hoffmann H-H, Bozzacco L, Garcia G, Gong D, Damoiseaux R, Tang H, Morizono K, Rudin CM, Sun R, Arumugaswami V, Poirier JT, MacDonald MR, Rice CM, Li MMH
JournalViruses
Volume13
Issue11
Date Published2021 Oct 20
ISSN1999-4915
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.

DOI10.3390/v13112113
Alternate JournalViruses
PubMed ID34834920
PubMed Central IDPMC8623001
Grant ListSeed Grant / / Jonsson Comprehensive Cancer Center /
R01 AI145044 / AI / NIAID NIH HHS / United States
Core Voucher Award / / Clinical and Translational Science Institute, University of California, Los Angeles /
Faculty Seed Grant CRN-20-637544 / / Cancer Research Coordinating Committee /
R01AI158704 / / National Institute of Allergy and Infectious Diseases /
U19 AI149504 / AI / NIAID NIH HHS / United States
P30 CA016042 / CA / NCI NIH HHS / United States
P30 AI028697 / AI / NIAID NIH HHS / United States

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