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Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

We sequenced the genomes of 5,085 SARS-CoV-2 strains causing two COVID-19 disease waves in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston, and an ongoing massi...

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Autores principales: Long, S. Wesley, Olsen, Randall J., Christensen, Paul A., Bernard, David W., Davis, James J., Shukla, Maulik, Nguyen, Marcus, Saavedra, Matthew Ojeda, Yerramilli, Prasanti, Pruitt, Layne, Subedi, Sishir, Kuo, Hung-Che, Hendrickson, Heather, Eskandari, Ghazaleh, Nguyen, Hoang A. T., Long, J. Hunter, Kumaraswami, Muthiah, Goike, Jule, Boutz, Daniel, Gollihar, Jimmy, McLellan, Jason S., Chou, Chia-Wei, Javanmardi, Kamyab, Finkelstein, Ilya J., Musser, James M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536878/
https://www.ncbi.nlm.nih.gov/pubmed/33024977
http://dx.doi.org/10.1101/2020.09.22.20199125
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author Long, S. Wesley
Olsen, Randall J.
Christensen, Paul A.
Bernard, David W.
Davis, James J.
Shukla, Maulik
Nguyen, Marcus
Saavedra, Matthew Ojeda
Yerramilli, Prasanti
Pruitt, Layne
Subedi, Sishir
Kuo, Hung-Che
Hendrickson, Heather
Eskandari, Ghazaleh
Nguyen, Hoang A. T.
Long, J. Hunter
Kumaraswami, Muthiah
Goike, Jule
Boutz, Daniel
Gollihar, Jimmy
McLellan, Jason S.
Chou, Chia-Wei
Javanmardi, Kamyab
Finkelstein, Ilya J.
Musser, James M.
author_facet Long, S. Wesley
Olsen, Randall J.
Christensen, Paul A.
Bernard, David W.
Davis, James J.
Shukla, Maulik
Nguyen, Marcus
Saavedra, Matthew Ojeda
Yerramilli, Prasanti
Pruitt, Layne
Subedi, Sishir
Kuo, Hung-Che
Hendrickson, Heather
Eskandari, Ghazaleh
Nguyen, Hoang A. T.
Long, J. Hunter
Kumaraswami, Muthiah
Goike, Jule
Boutz, Daniel
Gollihar, Jimmy
McLellan, Jason S.
Chou, Chia-Wei
Javanmardi, Kamyab
Finkelstein, Ilya J.
Musser, James M.
author_sort Long, S. Wesley
collection PubMed
description We sequenced the genomes of 5,085 SARS-CoV-2 strains causing two COVID-19 disease waves in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston, and an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotypes and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein - the primary target of global vaccine efforts - are replete with amino acid replacements, perhaps indicating the action of selection. We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR30022. Our study is the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves, and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution.
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spelling pubmed-75368782020-10-07 Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area Long, S. Wesley Olsen, Randall J. Christensen, Paul A. Bernard, David W. Davis, James J. Shukla, Maulik Nguyen, Marcus Saavedra, Matthew Ojeda Yerramilli, Prasanti Pruitt, Layne Subedi, Sishir Kuo, Hung-Che Hendrickson, Heather Eskandari, Ghazaleh Nguyen, Hoang A. T. Long, J. Hunter Kumaraswami, Muthiah Goike, Jule Boutz, Daniel Gollihar, Jimmy McLellan, Jason S. Chou, Chia-Wei Javanmardi, Kamyab Finkelstein, Ilya J. Musser, James M. medRxiv Article We sequenced the genomes of 5,085 SARS-CoV-2 strains causing two COVID-19 disease waves in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston, and an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotypes and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein - the primary target of global vaccine efforts - are replete with amino acid replacements, perhaps indicating the action of selection. We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR30022. Our study is the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves, and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution. Cold Spring Harbor Laboratory 2020-09-29 /pmc/articles/PMC7536878/ /pubmed/33024977 http://dx.doi.org/10.1101/2020.09.22.20199125 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/It is made available under a CC-BY-NC-ND 4.0 International license (http://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Article
Long, S. Wesley
Olsen, Randall J.
Christensen, Paul A.
Bernard, David W.
Davis, James J.
Shukla, Maulik
Nguyen, Marcus
Saavedra, Matthew Ojeda
Yerramilli, Prasanti
Pruitt, Layne
Subedi, Sishir
Kuo, Hung-Che
Hendrickson, Heather
Eskandari, Ghazaleh
Nguyen, Hoang A. T.
Long, J. Hunter
Kumaraswami, Muthiah
Goike, Jule
Boutz, Daniel
Gollihar, Jimmy
McLellan, Jason S.
Chou, Chia-Wei
Javanmardi, Kamyab
Finkelstein, Ilya J.
Musser, James M.
Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area
title Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area
title_full Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area
title_fullStr Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area
title_full_unstemmed Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area
title_short Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area
title_sort molecular architecture of early dissemination and massive second wave of the sars-cov-2 virus in a major metropolitan area
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536878/
https://www.ncbi.nlm.nih.gov/pubmed/33024977
http://dx.doi.org/10.1101/2020.09.22.20199125
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