A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition

M. Eugenia Dieterle; Denise Haslwanter; Robert H. Bortz; Ariel S. Wirchnianski; Gorka Lasso; Olivia Vergnolle; Shawn A. Abbasi; J. Maximilian Fels; Ethan Laudermilch; Catalina Florez; Amanda Mengotto; Duncan Kimmel; Ryan J. Malonis; George Georgiev; Jose Quiroz; Jason Barnhill; Liise anne Pirofski; Johanna P. Daily; John M. Dye; Jonathan R. Lai; Andrew S. Herbert; Kartik Chandran; Rohit K. Jangra

doi:10.1016/j.chom.2020.06.020

A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition

M. Eugenia Dieterle, Denise Haslwanter, Robert H. Bortz, Ariel S. Wirchnianski, Gorka Lasso, Olivia Vergnolle, Shawn A. Abbasi, J. Maximilian Fels, Ethan Laudermilch, Catalina Florez, Amanda Mengotto, Duncan Kimmel, Ryan J. Malonis, George Georgiev, Jose Quiroz, Jason Barnhill, Liise anne Pirofski, Johanna P. Daily, John M. Dye, Jonathan R. LaiAndrew S. Herbert, Kartik Chandran, Rohit K. Jangra

Research output: Contribution to journal › Article › peer-review

121 Scopus citations

Abstract

There is an urgent need for vaccines and therapeutics to prevent and treat COVID-19. Rapid SARS-CoV-2 countermeasure development is contingent on the availability of robust, scalable, and readily deployable surrogate viral assays to screen antiviral humoral responses, define correlates of immune protection, and down-select candidate antivirals. Here, we generate a highly infectious recombinant vesicular stomatitis virus (VSV) bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein and show that this recombinant virus, rVSV-SARS-CoV-2 S, closely resembles SARS-CoV-2 in its entry-related properties. The neutralizing activities of a large panel of COVID-19 convalescent sera can be assessed in a high-throughput fluorescent reporter assay with rVSV-SARS-CoV-2 S, and neutralization of rVSV-SARS-CoV-2 S and authentic SARS-CoV-2 by spike-specific antibodies in these antisera is highly correlated. Our findings underscore the utility of rVSV-SARS-CoV-2 S for the development of spike-specific therapeutics and for mechanistic studies of viral entry and its inhibition.

Original language	English (US)
Pages (from-to)	486-496.e6
Journal	Cell Host and Microbe
Volume	28
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2020.06.020
State	Published - Sep 9 2020

Keywords

ACE2
COVID-19
SARS-CoV-2
VSV
antiviral drugs
convalescent plasma
neutralization assay
neutralizing antibody
serology
surrogate

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chom.2020.06.020

Cite this

Dieterle, M. E., Haslwanter, D., Bortz, R. H., Wirchnianski, A. S., Lasso, G., Vergnolle, O., Abbasi, S. A., Fels, J. M., Laudermilch, E., Florez, C., Mengotto, A., Kimmel, D., Malonis, R. J., Georgiev, G., Quiroz, J., Barnhill, J., Pirofski, L. A., Daily, J. P., Dye, J. M., ... Jangra, R. K. (2020). A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition. Cell Host and Microbe, 28(3), 486-496.e6. https://doi.org/10.1016/j.chom.2020.06.020

Dieterle, ME, Haslwanter, D, Bortz, RH, Wirchnianski, AS, Lasso, G, Vergnolle, O, Abbasi, SA, Fels, JM, Laudermilch, E, Florez, C, Mengotto, A, Kimmel, D, Malonis, RJ, Georgiev, G, Quiroz, J, Barnhill, J, Pirofski, LA , Daily, JP, Dye, JM, Lai, JR, Herbert, AS, Chandran, K & Jangra, RK 2020, 'A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition', Cell Host and Microbe, vol. 28, no. 3, pp. 486-496.e6. https://doi.org/10.1016/j.chom.2020.06.020

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abstract = "There is an urgent need for vaccines and therapeutics to prevent and treat COVID-19. Rapid SARS-CoV-2 countermeasure development is contingent on the availability of robust, scalable, and readily deployable surrogate viral assays to screen antiviral humoral responses, define correlates of immune protection, and down-select candidate antivirals. Here, we generate a highly infectious recombinant vesicular stomatitis virus (VSV) bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein and show that this recombinant virus, rVSV-SARS-CoV-2 S, closely resembles SARS-CoV-2 in its entry-related properties. The neutralizing activities of a large panel of COVID-19 convalescent sera can be assessed in a high-throughput fluorescent reporter assay with rVSV-SARS-CoV-2 S, and neutralization of rVSV-SARS-CoV-2 S and authentic SARS-CoV-2 by spike-specific antibodies in these antisera is highly correlated. Our findings underscore the utility of rVSV-SARS-CoV-2 S for the development of spike-specific therapeutics and for mechanistic studies of viral entry and its inhibition.",

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AU - Bortz, Robert H.

AU - Wirchnianski, Ariel S.

AU - Lasso, Gorka

AU - Vergnolle, Olivia

AU - Abbasi, Shawn A.

AU - Fels, J. Maximilian

AU - Laudermilch, Ethan

AU - Florez, Catalina

AU - Mengotto, Amanda

AU - Kimmel, Duncan

AU - Malonis, Ryan J.

AU - Georgiev, George

AU - Quiroz, Jose

AU - Barnhill, Jason

AU - Pirofski, Liise anne

AU - Daily, Johanna P.

AU - Dye, John M.

AU - Lai, Jonathan R.

AU - Herbert, Andrew S.

AU - Chandran, Kartik

AU - Jangra, Rohit K.

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A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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