ArticlePLoS biology2021
SARS-CoV-2 variants reveal features critical for replication in primary human cells.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- The conserved QTQTX motif in the SARS-CoV-2 spike protein is dispensable for cleavage and lung cell entry of the emerging variant BA.3.2.Journal of virology · 2026Article
- Intra-patient neuraminidase mutations in avian H5N1 influenza virus reduce sialidase activity to complement weaker hemagglutinin binding and facilitate human infection.PLoS pathogens · 2026Article
- Activity and cellular distribution of ORF3a mutants of SARS-CoV-2 variants of concern.The Journal of general virology · 2025Article
- Substitution-Mutation Rate Ratio (c/µ) As Molecular Adaptation Test Beyond Ka/Ks: A SARS-COV-2 Case Study.Journal of molecular evolution · 2025Article
- An inactivated SARS-CoV-2 vaccine based on a Vero cell culture-adapted high-titer virus confers cross-protection in small animals.Scientific reports · 2024Article
- Cell culture systems for isolation of SARS-CoV-2 clinical isolates and generation of recombinant virus.iScience · 2023Article
- Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants.Viruses · 2023Article
- Cryo-EM reveals binding of linoleic acid to SARS-CoV-2 spike glycoprotein, suggesting an antiviral treatment strategy.Acta crystallographica. Section D, Structural biology · 2023Article
- Immunoinformatic exploration of a multi-epitope-based peptide vaccine candidate targeting emerging variants of SARS-CoV-2.Frontiers in microbiology · 2023Article
- CoVEffect: interactive system for mining the effects of SARS-CoV-2 mutations and variants based on deep learning.GigaScience · 2022Article
- A pseudovirus-based platform to measure neutralizing antibodies in Mexico using SARS-CoV-2 as proof-of-concept.Scientific reports · 2022Article
- Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Exhaled Aerosols and Efficacy of Masks During Early Mild Infection.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Sec61 Inhibitor Apratoxin S4 Potently Inhibits SARS-CoV-2 and Exhibits Broad-Spectrum Antiviral Activity.ACS infectious diseases · 2022Article
- Article
- Comparison among plaque assay, tissue culture infectious dose (TCIDIranian journal of microbiology · 2022Article
- COVID-19: the case for aerosol transmission.Interface focus · 2022Review
- Emerging SARS-CoV-2 variants can potentially break set epidemiological barriers in COVID-19.Journal of medical virology · 2022Review
- A highly immunogenic live-attenuated vaccine candidate prevents SARS-CoV-2 infection and transmission in hamsters.Innovation (Cambridge (Mass.)) · 2022Article
- Restriction factor screening identifies RABGAP1L-mediated disruption of endocytosis as a host antiviral defense.Cell reports · 2022Article
- Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since entering the human population, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; the causative agent of Coronavirus Disease 2019 [COVID-19]) has spread worldwide, causing >100 million infections and >2 million deaths. While large-scale sequencing efforts have identified numerous genetic variants in SARS-CoV-2 during its circulation, it remains largely unclear whether many of these changes impact adaptation, replication, or transmission of the virus. Here, we characterized 14 different low-passage replication-competent human SARS-CoV-2 isolates representing all major European clades observed during the first pandemic wave in early 2020. By integrating viral sequencing data from patient material, virus stocks, and passaging experiments, together with kinetic virus replication data from nonhuman Vero-CCL81 cells and primary differentiated human bronchial epithelial cells (BEpCs), we observed several SARS-CoV-2 features that associate with distinct phenotypes. Notably, naturally occurring variants in Orf3a (Q57H) and nsp2 (T85I) were associated with poor replication in Vero-CCL81 cells but not in BEpCs, while SARS-CoV-2 isolates expressing the Spike D614G variant generally exhibited enhanced replication abilities in BEpCs. Strikingly, low-passage Vero-derived stock preparation of 3 SARS-CoV-2 isolates selected for substitutions at positions 5/6 of E and were highly attenuated in BEpCs, revealing a key cell-specific function to this region. Rare isolate-specific deletions were also observed in the Spike furin cleavage site during Vero-CCL81 passage, but these were rapidly selected against in BEpCs, underscoring the importance of this site for SARS-CoV-2 replication in primary human cells. Overall, our study uncovers sequence features in SARS-CoV-2 variants that determine cell-specific replication and highlights the need to monitor SARS-CoV-2 stocks carefully when phenotyping newly emerging variants or potential variants of concern.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.