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A CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry.
Luu, Anh Phuong; Yao, Zhenlan; Ramachandran, Sangeetha; Azzopardi, Stephanie A; Miles, Linde A; Schneider, William M; Hoffmann, H-Heinrich; Bozzacco, Leonia; Garcia, Gustavo; Gong, Danyang; Damoiseaux, Robert; Tang, Hengli; Morizono, Kouki; Rudin, Charles M; Sun, Ren; Arumugaswami, Vaithilingaraja; Poirier, John T; MacDonald, Margaret R; Rice, Charles M; Li, Melody M H.
Affiliation
  • Luu AP; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Yao Z; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Ramachandran S; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
  • Azzopardi SA; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • Miles LA; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Schneider WM; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • Hoffmann HH; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • Bozzacco L; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • Garcia G; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
  • Gong D; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
  • Damoiseaux R; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
  • Tang H; California NanoSystems Institute, University of California, Los Angeles, CA 90095, USA.
  • Morizono K; Department of Bioengineering, Samueli School of Engineering, University of California, Los Angeles, CA 90095, USA.
  • Rudin CM; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA.
  • Sun R; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
  • Arumugaswami V; Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Poirier JT; AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • MacDonald MR; Druckenmiller Center for Lung Cancer Research and Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Rice CM; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
  • Li MMH; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
Viruses ; 13(11)2021 10 20.
Article in En | MEDLINE | ID: mdl-34834920
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: GTP-Binding Proteins / RhoB GTP-Binding Protein / Zika Virus / Zika Virus Infection / Neoplasm Proteins Type of study: Prognostic_studies Limits: Humans Language: En Journal: Viruses Year: 2021 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: GTP-Binding Proteins / RhoB GTP-Binding Protein / Zika Virus / Zika Virus Infection / Neoplasm Proteins Type of study: Prognostic_studies Limits: Humans Language: En Journal: Viruses Year: 2021 Document type: Article