Your browser doesn't support javascript.
A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike.
Dadonaite, Bernadeta; Crawford, Katharine H D; Radford, Caelan E; Farrell, Ariana G; Yu, Timothy C; Hannon, William W; Zhou, Panpan; Andrabi, Raiees; Burton, Dennis R; Liu, Lihong; Ho, David D; Chu, Helen Y; Neher, Richard A; Bloom, Jesse D.
  • Dadonaite B; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Crawford KHD; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Genome Sciences & Medical Scientist Training Program, University of Washington, Seattle, WA 98109, USA.
  • Radford CE; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98109, USA.
  • Farrell AG; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
  • Yu TC; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98109, USA.
  • Hannon WW; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98109, USA.
  • Zhou P; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
  • Andrabi R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
  • Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
  • Liu L; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Ho DD; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Division of Infectious Diseases, Department of Me
  • Chu HY; University of Washington, Department of Medicine, Division of Allergy and Infectious Diseases, Seattle, WA, USA.
  • Neher RA; Biozentrum, University of Basel, Basel, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Bloom JD; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA. Electronic address: jbloom@fredhutch.org.
Cell ; 186(6): 1263-1278.e20, 2023 03 16.
Article in English | MEDLINE | ID: covidwho-2229215
ABSTRACT
A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Viruses / COVID-19 Topics: Variants Limits: Humans Language: English Journal: Cell Year: 2023 Document Type: Article Affiliation country: J.cell.2023.02.001

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA Viruses / COVID-19 Topics: Variants Limits: Humans Language: English Journal: Cell Year: 2023 Document Type: Article Affiliation country: J.cell.2023.02.001