Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants.

Autor: Taylor MK; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Williams EP; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Xue Y; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Jenjaroenpun P; Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Wongsurawat T; Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Smith AP; Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN 38103, USA., Smith AM; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.; Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN 38103, USA.; Institute for the Study of Host-Pathogen Systems, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Parvathareddy J; Regional Biocontainment Laboratory, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Kong Y; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Vogel P; Veterinary Pathology Core Laboratory, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Cao X; Department of Health Promotion and Disease Prevention, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Reichard W; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Spruill-Harrell B; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA., Samarasinghe AE; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.; Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN 38103, USA., Nookaew I; Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Fitzpatrick EA; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.; Institute for the Study of Host-Pathogen Systems, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Smith MD; Center for Molecular Biophysics, University of Tennessee-Oak Ridge National Laboratory, Knoxville, TN 37996, USA.; Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee- Knoxville, Knoxville, TN 37996, USA., Aranha M; Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee- Knoxville, Knoxville, TN 37996, USA., Smith JC; Center for Molecular Biophysics, University of Tennessee-Oak Ridge National Laboratory, Knoxville, TN 37996, USA.; Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee- Knoxville, Knoxville, TN 37996, USA., Jonsson CB; Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.; Institute for the Study of Host-Pathogen Systems, University of Tennessee Health Science Center, Memphis, TN 38163, USA.; Regional Biocontainment Laboratory, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2023 Feb 23; Vol. 15 (3). Date of Electronic Publication: 2023 Feb 23.
DOI: 10.3390/v15030611
Abstrakt: The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic. Mathematical modeling of the lung viral replication of four clinical isolates showed a dichotomy between two B.1. isolates with significantly faster and slower infected cell clearance rates, respectively. While isolates induced several common immune host responses to infection, one B.1 isolate was unique in the promotion of eosinophil-associated proteins IL-5 and CCL11. Moreover, its mortality rate was significantly slower. Lung microscopic histopathology suggested further phenotypic divergence among the five isolates showing three distinct sets of phenotypes: (i) consolidation, alveolar hemorrhage, and inflammation, (ii) interstitial inflammation/septal thickening and peribronchiolar/perivascular lymphoid cells, and (iii) consolidation, alveolar involvement, and endothelial hypertrophy/margination. Together these findings show divergence in the phenotypic outcomes of these clinical isolates and reveal the potential importance of nonsynonymous mutations in nsp2 and ORF8.
Databáze: MEDLINE
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