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A defective viral genome strategy elicits broad protective immunity against respiratory viruses.
Xiao, Yinghong; Lidsky, Peter V; Shirogane, Yuta; Aviner, Ranen; Wu, Chien-Ting; Li, Weiyi; Zheng, Weihao; Talbot, Dale; Catching, Adam; Doitsh, Gilad; Su, Weiheng; Gekko, Colby E; Nayak, Arabinda; Ernst, Joel D; Brodsky, Leonid; Brodsky, Elia; Rousseau, Elsa; Capponi, Sara; Bianco, Simone; Nakamura, Robert; Jackson, Peter K; Frydman, Judith; Andino, Raul.
  • Xiao Y; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Lidsky PV; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Shirogane Y; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
  • Aviner R; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biology and Genetics, Stanford University, Stanford, CA 94305, USA.
  • Wu CT; Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University, Stanford, CA 94305, USA.
  • Li W; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Zheng W; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
  • Talbot D; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Aleph Therapeutics, Inc., Stanford, CA 94305, USA.
  • Catching A; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Doitsh G; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Su W; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; School of Life Sciences, Jilin University, Changchun, China.
  • Gekko CE; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Nayak A; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biology and Genetics, Stanford University, Stanford, CA 94305, USA.
  • Ernst JD; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
  • Brodsky L; Tauber Bioinformatics Research Center and Department of Evolutionary & Environmental Biology, University of Haifa, Mount Carmel, Haifa 31905, Israel.
  • Brodsky E; Pine Biotech Inc., New Orleans, LA 70112, USA.
  • Rousseau E; Functional Genomics and Cellular Engineering, AI and Cognitive Software, IBM Almaden Research Center, San Jose, CA 95120, USA.
  • Capponi S; Functional Genomics and Cellular Engineering, AI and Cognitive Software, IBM Almaden Research Center, San Jose, CA 95120, USA.
  • Bianco S; Functional Genomics and Cellular Engineering, AI and Cognitive Software, IBM Almaden Research Center, San Jose, CA 95120, USA.
  • Nakamura R; Aleph Therapeutics, Inc., Stanford, CA 94305, USA.
  • Jackson PK; Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University, Stanford, CA 94305, USA.
  • Frydman J; Department of Biology and Genetics, Stanford University, Stanford, CA 94305, USA.
  • Andino R; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: raul.andino@ucsf.edu.
Cell ; 184(25): 6037-6051.e14, 2021 12 09.
Article in English | MEDLINE | ID: covidwho-1520752
ABSTRACT
RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short- and long-term protection against SARS-CoV-2 and other respiratory infections in animal models.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Replication / Capsid Proteins / Defective Interfering Viruses Type of study: Randomized controlled trials Limits: Animals / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.11.023

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Replication / Capsid Proteins / Defective Interfering Viruses Type of study: Randomized controlled trials Limits: Animals / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.11.023