Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein

Individuals infected with the SARS-CoV-2 Delta variant, lineage B.1.617.2, exhibit faster initial infection with a higher viral load than prior variants, and pseudotyped viral particles bearing the SARS-CoV-2 Delta variant spike protein induce a faster initial infection rate of target cells compared...

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Main Authors: Jennifer D. Petersen, Jianming Lu, Wendy Fitzgerald, Fei Zhou, Paul S. Blank, Doreen Matthies, Joshua Zimmerberg
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/5/1024
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author Jennifer D. Petersen
Jianming Lu
Wendy Fitzgerald
Fei Zhou
Paul S. Blank
Doreen Matthies
Joshua Zimmerberg
author_facet Jennifer D. Petersen
Jianming Lu
Wendy Fitzgerald
Fei Zhou
Paul S. Blank
Doreen Matthies
Joshua Zimmerberg
author_sort Jennifer D. Petersen
collection DOAJ
description Individuals infected with the SARS-CoV-2 Delta variant, lineage B.1.617.2, exhibit faster initial infection with a higher viral load than prior variants, and pseudotyped viral particles bearing the SARS-CoV-2 Delta variant spike protein induce a faster initial infection rate of target cells compared to those bearing other SARS-CoV-2 variant spikes. Here, we show that pseudotyped viral particles bearing the Delta variant spike form unique aggregates, as evidenced by negative stain and cryogenic electron microscopy (EM), flow cytometry, and nanoparticle tracking analysis. Viral particles pseudotyped with other SARS-CoV-2 spike variants do not show aggregation by any of these criteria. The contribution to infection kinetics of the Delta spike’s unique property to aggregate is discussed with respect to recent evidence for collective infection by other viruses. Irrespective of this intriguing possibility, spike-dependent aggregation is a new functional parameter of spike-expressing viral particles to evaluate in future spike protein variants.
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spelling doaj.art-48368d7cd6564878a6df64cdceff7ee82023-11-23T13:32:00ZengMDPI AGViruses1999-49152022-05-01145102410.3390/v14051024Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike ProteinJennifer D. Petersen0Jianming Lu1Wendy Fitzgerald2Fei Zhou3Paul S. Blank4Doreen Matthies5Joshua Zimmerberg6Section on Integrative Biophysics, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USACodex BioSolutions, Inc., Department of Research and Development, Cell Biology, 12358 Parklawn Dr., Suite 250, North Bethesda, MD 20852, USASection on Intercellular Interactions, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USAUnit on Structural Biology, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USASection on Integrative Biophysics, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USAUnit on Structural Biology, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USASection on Integrative Biophysics, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USAIndividuals infected with the SARS-CoV-2 Delta variant, lineage B.1.617.2, exhibit faster initial infection with a higher viral load than prior variants, and pseudotyped viral particles bearing the SARS-CoV-2 Delta variant spike protein induce a faster initial infection rate of target cells compared to those bearing other SARS-CoV-2 variant spikes. Here, we show that pseudotyped viral particles bearing the Delta variant spike form unique aggregates, as evidenced by negative stain and cryogenic electron microscopy (EM), flow cytometry, and nanoparticle tracking analysis. Viral particles pseudotyped with other SARS-CoV-2 spike variants do not show aggregation by any of these criteria. The contribution to infection kinetics of the Delta spike’s unique property to aggregate is discussed with respect to recent evidence for collective infection by other viruses. Irrespective of this intriguing possibility, spike-dependent aggregation is a new functional parameter of spike-expressing viral particles to evaluate in future spike protein variants.https://www.mdpi.com/1999-4915/14/5/1024coronavirusSARS-CoV-2pseudotyped viral particlespike proteinvariantaggregation
spellingShingle Jennifer D. Petersen
Jianming Lu
Wendy Fitzgerald
Fei Zhou
Paul S. Blank
Doreen Matthies
Joshua Zimmerberg
Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein
Viruses
coronavirus
SARS-CoV-2
pseudotyped viral particle
spike protein
variant
aggregation
title Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein
title_full Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein
title_fullStr Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein
title_full_unstemmed Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein
title_short Unique Aggregation of Retroviral Particles Pseudotyped with the Delta Variant SARS-CoV-2 Spike Protein
title_sort unique aggregation of retroviral particles pseudotyped with the delta variant sars cov 2 spike protein
topic coronavirus
SARS-CoV-2
pseudotyped viral particle
spike protein
variant
aggregation
url https://www.mdpi.com/1999-4915/14/5/1024
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