Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area
| Autor: | James J. Davis, Ghazaleh Eskandari, Daniel R. Boutz, Layne Pruitt, James M. Musser, Maulik Shukla, Jason S. McLellan, Chia Wei Chou, Marcus Nguyen, Jimmy Gollihar, J. Hunter Long, Muthiah Kumaraswami, Jule Goike, David W. Bernard, Sishir Subedi, Heather Hendrickson, S. Wesley Long, Kamyab Javanmardi, Prasanti Yerramilli, Matthew Ojeda Saavedra, Randall J. Olsen, Hung-Che Kuo, Ilya J. Finkelstein, Paul A. Christensen, Hoang A. T. Nguyen |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular viruses Viral Nonstructural Proteins medicine.disease_cause Genome Machine Learning Clinical Science and Epidemiology COVID-19 Testing 0302 clinical medicine Sequence Analysis Protein Genotype Pandemic 030212 general & internal medicine skin and connective tissue diseases Phylogeny Coronavirus Infectivity education.field_of_study 0303 health sciences Coronavirus RNA-Dependent RNA Polymerase Transmission (medicine) virus diseases Texas QR1-502 3. Good health genome sequencing Molecular Diagnostic Techniques Spike Glycoprotein Coronavirus Coronavirus Infections Research Article Pneumonia Viral Population Virulence Genome Viral Biology Microbiology Article Virus Betacoronavirus 03 medical and health sciences Immune system Virology evolution medicine Humans Amino Acid Sequence education Pandemics COVID-19 disease 030304 developmental biology Base Sequence molecular population genomics Clinical Laboratory Techniques SARS-CoV-2 fungi COVID-19 RNA-Dependent RNA Polymerase Antibodies Neutralizing body regions Amino Acid Substitution |
| Zdroj: | mBio medRxiv article-version (status) pre article-version (number) 3 mBio, Vol 11, Iss 6 (2020) |
| Popis: | There is concern about second and subsequent waves of COVID-19 caused by the SARS-CoV-2 coronavirus occurring in communities globally that had an initial disease wave. Metropolitan Houston, TX, with a population of 7 million, is experiencing a massive second disease wave that began in late May 2020. To understand SARS-CoV-2 molecular population genomic architecture and evolution and the relationship between virus genotypes and patient features, we sequenced the genomes of 5,085 SARS-CoV-2 strains from these two waves. Our report provides the first molecular characterization of SARS-CoV-2 strains causing two distinct COVID-19 disease waves. We sequenced the genomes of 5,085 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains causing two coronavirus disease 2019 (COVID-19) disease waves in metropolitan Houston, TX, an ethnically diverse region with 7 million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston and from viruses recovered in 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 genotype 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 CR3022. Our report represents 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. |
| Databáze: | OpenAIRE |
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