Cell type-specific adaptation of the SARS-CoV-2 spike

Virus Evolution, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 1, 2024

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can infect various human tissues and cell types, principally via interaction with its cognate receptor angiotensin-converting enzyme-2 (ACE2). However, how the virus evolves in different cellular environments is poorly understood. Here, we used experimental evolution to study adaptation of SARS-CoV-2 spike four lines expressing levels key entry factors. After twenty passages a spike-expressing recombinant vesicular stomatitis (VSV), cell-type-specific phenotypic changes were observed sequencing allowed identification sixteen adaptive mutations. We VSV pseudotyping measure efficiency, ACE2 affinity, processing, TMPRSS2 usage, pathway usage all mutants, alone or combination. The fusogenicity mutant spikes was assessed cell-cell fusion assay. Finally, VSVs fitness advantage associated selected found that effects these mutations varied across both terms viral replicative fitness. Interestingly, two (L48S A372T) emerged cells low increased syncytia induction, efficiency under low-ACE2 conditions. Our results demonstrate specific types have implications for understanding tissue tropism evolution.

Language: Английский

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Insights into the Replication Kinetics Profiles of Malaysian SARS-CoV-2 Variant Alpha, Beta, Delta, and Omicron in Vero E6 cell line

Published: Aug. 13, 2024

Comprehending the replication kinetics of SARS-CoV-2 variants helps explain why certain var-iants spread more easily and are contagious, pose significant health menaces to global populations. The Malaysian isolates Alpha, Beta, Delta, Omicron were studied in Vero E6 cell line. Their deter-mined using plaque assay, quantitative real-time PCR (qRT-PCR), viral growth curve. Beta variant exhibited highest rate at 24 hours post-infection (h.p.i), as evi-denced by titers lowest RNA multiplication threshold. phenotypes also varied among variants, which formed largest smallest plaques, respectively. All showed strong cytopathic effects after 48 h.p.i. whole-genome sequencing highlighted cell-culture adaptation, where Delta acquired mutations multibasic cleavage site three cycles passaging. findings suggest a link between rates their respec-tive transmissibility pathogenicity. This is essential predicting impacts upcom-ing on local populations useful designing preventive measures curb virus outbreaks.

Language: Английский

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Insights into the Replication Kinetics Profiles of Malaysian SARS-CoV-2 Variant Alpha, Beta, Delta, and Omicron in Vero E6 Cell Line

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10541 - 10541

Published: Sept. 30, 2024

Comprehending the replication kinetics of SARS-CoV-2 variants helps explain why certain spread more easily, are contagious, and pose a significant health menace to global populations. The Malaysian isolates Alpha, Beta, Delta, Omicron were studied in Vero E6 cell line. Their determined using plaque assay, quantitative real-time PCR (qRT-PCR), viral growth curve. Beta variant exhibited highest rate at 24 h post-infection (h.p.i), as evidenced by titers lowest RNA multiplication threshold. phenotypes also varied among variants, which formed largest smallest plaques, respectively. All showed strong cytopathic effects after 48 h.p.i. whole-genome sequencing highlighted cell-culture adaptation, where acquired mutations multibasic cleavage site three cycles passaging. findings suggest link between rates their respective transmissibility pathogenicity. This is essential predicting impacts upcoming on local populations useful designing preventive measures curb virus outbreaks.

Language: Английский

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Relevance of the Entry by Fusion at the Cytoplasmic Membrane vs. Fusion After Endocytosis in the HIV and SARS-Cov-2 Infections

Results and problems in cell differentiation, Journal Year: 2023, Volume and Issue: unknown, P. 329 - 344

Published: Nov. 23, 2023

Language: Английский

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Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 29, 2023

ABSTRACT The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane during virus entry and part a broadly neutralizing epitope. However, sequence determinants at the its adjacent regions pathogenicity antigenicity remain elusive. In this study, we performed series deep mutational scanning (DMS) experiments on an S2 region spanning authentic in different cell lines presence antibodies. We identified mutations residue 813 that reduced TMPRSS2-mediated with decreased virulence. addition, showed F823Y mutation, present bat betacoronavirus HKU9 protein, confers resistance to Our findings provide mechanistic insights into also highlight potential challenge developing protective S2-based coronavirus vaccines.

Language: Английский

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