The Delta variant SARS-CoV-2 spike protein uniquely promotes aggregation of pseudotyped viral particles
Preprint
- 8 April 2022
- preprint
- research article
- Published by Cold Spring Harbor Laboratory
Abstract
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 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 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.Keywords
This publication has 56 references indexed in Scilit:
- Structure, Function, and Evolution of Coronavirus Spike ProteinsAnnual Review of Virology, 2016
- Murine Leukemia Virus (MLV)-based Coronavirus Spike-pseudotyped Particle Production and InfectionBio-Protocol, 2016
- Coronaviruses: An Overview of Their Replication and PathogenesisPublished by Springer Science and Business Media LLC ,2015
- Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike proteinProceedings of the National Academy of Sciences of the United States of America, 2014
- Intracellular assembly and budding of the Murine Leukemia Virus in infected cellsRetrovirology, 2006
- Automated electron microscope tomography using robust prediction of specimen movementsJournal of Structural Biology, 2005
- Retroviral Vectors Pseudotyped with Severe Acute Respiratory Syndrome Coronavirus S ProteinJournal of Virology, 2004
- The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core ComplexJournal of Virology, 2003
- Supramolecular organization of immature and mature murine leukemia virus revealed by electron cryo-microscopy: Implications for retroviral assembly mechanismsProceedings of the National Academy of Sciences of the United States of America, 1998
- The Pathway of Membrane Fusion Catalyzed by Influenza Hemagglutinin: Restriction of Lipids, Hemifusion, and Lipidic Fusion Pore FormationThe Journal of cell biology, 1998