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Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission.
Escalera, Alba; Gonzalez-Reiche, Ana S; Aslam, Sadaf; Mena, Ignacio; Laporte, Manon; Pearl, Rebecca L; Fossati, Andrea; Rathnasinghe, Raveen; Alshammary, Hala; van de Guchte, Adriana; Farrugia, Keith; Qin, Yiren; Bouhaddou, Mehdi; Kehrer, Thomas; Zuliani-Alvarez, Lorena; Meekins, David A; Balaraman, Velmurugan; McDowell, Chester; Richt, Jürgen A; Bajic, Goran; Sordillo, Emilia Mia; Dejosez, Marion; Zwaka, Thomas P; Krogan, Nevan J; Simon, Viviana; Albrecht, Randy A; van Bakel, Harm; García-Sastre, Adolfo; Aydillo, Teresa.
  • Escalera A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, N
  • Gonzalez-Reiche AS; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Aslam S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Mena I; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Laporte M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Pearl RL; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Fossati A; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; QBI Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, Univer
  • Rathnasinghe R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, N
  • Alshammary H; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • van de Guchte A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Farrugia K; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Qin Y; Huffington Center for Cell-based Research in Parkinson's Disease, Black Family Stem Cell Institute, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA.
  • Bouhaddou M; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; QBI Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, Univer
  • Kehrer T; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, N
  • Zuliani-Alvarez L; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; QBI Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, Univer
  • Meekins DA; Department of Diagnostic Medicine/Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
  • Balaraman V; Department of Diagnostic Medicine/Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
  • McDowell C; Department of Diagnostic Medicine/Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
  • Richt JA; Department of Diagnostic Medicine/Pathobiology and Center of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
  • Bajic G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Sordillo EM; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Dejosez M; Huffington Center for Cell-based Research in Parkinson's Disease, Black Family Stem Cell Institute, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA.
  • Zwaka TP; Huffington Center for Cell-based Research in Parkinson's Disease, Black Family Stem Cell Institute, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA.
  • Krogan NJ; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; QBI Coronavirus Research Group (QCRG), San Francisco, CA 94158, USA; J. David Gladstone Insti
  • Simon V; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Moun
  • Albrecht RA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • van Bakel H; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Moun
  • Aydillo T; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: teresa.aydillo-gomez@mssm.edu.
Cell Host Microbe ; 30(3): 373-387.e7, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1767977
ABSTRACT
SARS-CoV-2 lineages have diverged into highly prevalent variants termed "variants of concern" (VOCs). Here, we characterized emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand their impact on transmissibility and virus pathogenicity and fitness. We demonstrate that the substitution S655Y, represented in the gamma and omicron VOCs, enhances viral replication and spike protein cleavage. The S655Y substitution was transmitted more efficiently than its ancestor S655H in the hamster infection model and was able to outcompete S655H in the hamster model and in a human primary airway system. Finally, we analyzed a set of emerging SARS-CoV-2 variants to investigate how different sets of mutations may impact spike processing. All VOCs tested exhibited increased spike cleavage and fusogenic capacity. Taken together, our study demonstrates that the spike mutations present in VOCs that become epidemiologically prevalent in humans are linked to an increase in spike processing and virus transmission.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Variants Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Variants Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2022 Document Type: Article