SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus

Autores
Alkayyal, Almohanad A.; Ajina, Reham; Cacciabue, Marco Polo Domingo; Alkayyal, Aaesha A.; Saeedi, Nizar H.; Hussain Alshehry, Taofik; Kaboha, Feras; Alotaibi, Mohammed A.; Zaidan, Nada; Shah, Khalid; Alroqi, Fayhan; Bakur Mahmoud, Ahmad
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Despite recent advances in the research on oncolytic viruses (OVs), a better understanding of how to enhance their replication is key to improving their therapeutic index. Understanding viral replication is important to improve treatment outcomes based on enhanced viral spreading within the tumor milieu. The VSV-Δ51 oncolytic virus has been widely used as an anticancer agent with a high selectivity profile. In this study, we examined the role of the SARS-CoV-2 spike protein receptor-binding domain (RBD) in enhancing VSV-Δ51 viral production and oncolytic activity. To test this hypothesis, we first generated a novel VSV-Δ51 mutant that encoded the SARS-COV-2 RBD and compared viral spreading and viral yield between VSV-Δ51-RBD and VSV-Δ51 in vitro. Using the viral plaque assay, we demonstrated that the presence of the SARS-CoV-2 RBD in the VSV-Δ51 genome is associated with a significantly larger viral plaque surface area and significantly higher virus titers. Subsequently, using an ATP release-based assay, we demonstrated that the SARS-CoV-2 RBD could enhance VSV-Δ51 oncolytic activity in vitro. This observation was further supported using the B16F10 tumor model. These findings highlighted a novel use of the SARS-CoV-2 RBD as an anticancer agent.
Instituto de Biotecnología
Fil: Alkayyal, Almohanad A. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia Saudita
Fil: Alkayyal, Almohanad A. King Abdullah International Medical Research Center. Immunology Research Program; Arabia Saudita
Fil: Ajina, Reham. King Abdullah International Medical Research Center. Immunology Research Program; Arabia Saudita
Fil: Ajina, Reham. King Saud bin Abdulaziz University for Health Sciences. College of Applied Medical Sciences. Department of Clinical Laboratory Sciences; Arabia Saudita
Fil: Cacciabue, Marco Polo Domingo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Cacciabue, Marco Polo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cacciabue, Marco Polo Domingo. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentina
Fil: Alkayyal, Aaesha A. Taibah University. College of Medicine; Arabia Saudita
Fil: Saeedi, Nizar H. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia Saudita
Fil: Hussain Alshehry, Taofik. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia Saudita
Fil: Kaboha, Feras. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia Saudita
Fil: Alotaibi, Mohammed A. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia Saudita
Fil: Alotaibi, Mohammed A. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia Saudita
Fil: Zaidan, Nada. King Abdulaziz City for Science and Technology. Joint Centers of Excellence Program. 8King Abdulaziz City for Science and Technology-Brigham and Women's Hospital (KACST-BWH) Centre of Excellence for Biomedicine; Arabia Saudita
Fil: Shah, Khalid. Harvard Medical School. Brigham and Women’s Hospital. Center for Stem Cell and Translational Immunotherapy (CSTI); Estados Unidos
Fil: Shah, Khalid. Harvard Medical School. Brigham and Women’s Hospital. Department of Neurosurgery; Estados Unidos
Fil: Shah, Khalid. Harvard University. Harvard Stem Cell Institute; Estados Unidos
Fil: Alroqi, Fayhan. King Abdullah International Medical Research Center. Immunology Research Program; Arabia Saudita
Fil: Alroqi, Fayhan. Ministry of the National Guard. Department of Immunology; Arabia Saudita
Fil: Alroqi, Fayhan. King Saud bin Abdulaziz University for Health Sciences. Faculty of Medicine; Arabia Saudita
Fil: Bakur Mahmoud, Ahmad. Taibah University. College of Applied Medical Sciences; Arabia Saudita
Fil: Bakur Mahmoud, Ahmad. Taibah University. Strategic Research and Innovation Laboratories; Arabia Saudita
Fil: Bakur Mahmoud, Ahmad. King Abdullah International Medical Research Center. Immunology Research Program; Arabia Saudita
Fuente
Frontiers in Immunology 14 : 1082191 (Enero 2023)
Materia
Severe Acute Respiratory Syndrome Coronavirus 2
Oncology
Melanoma
Vesicular Stomatitis Virus
Coronavirus del Síndrome Respiratorio Agudo Arave 2
Oncología
Virus de la Estomatitis Vesicular
SARS-CoV-2
Viroterapia
Agente Anticancerígeno
Virotherapy
Anticancer Agent
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
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spelling SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virusAlkayyal, Almohanad A.Ajina, RehamCacciabue, Marco Polo DomingoAlkayyal, Aaesha A.Saeedi, Nizar H.Hussain Alshehry, TaofikKaboha, FerasAlotaibi, Mohammed A.Zaidan, NadaShah, KhalidAlroqi, FayhanBakur Mahmoud, AhmadSevere Acute Respiratory Syndrome Coronavirus 2OncologyMelanomaVesicular Stomatitis VirusCoronavirus del Síndrome Respiratorio Agudo Arave 2OncologíaVirus de la Estomatitis VesicularSARS-CoV-2ViroterapiaAgente AnticancerígenoVirotherapyAnticancer AgentDespite recent advances in the research on oncolytic viruses (OVs), a better understanding of how to enhance their replication is key to improving their therapeutic index. Understanding viral replication is important to improve treatment outcomes based on enhanced viral spreading within the tumor milieu. The VSV-Δ51 oncolytic virus has been widely used as an anticancer agent with a high selectivity profile. In this study, we examined the role of the SARS-CoV-2 spike protein receptor-binding domain (RBD) in enhancing VSV-Δ51 viral production and oncolytic activity. To test this hypothesis, we first generated a novel VSV-Δ51 mutant that encoded the SARS-COV-2 RBD and compared viral spreading and viral yield between VSV-Δ51-RBD and VSV-Δ51 in vitro. Using the viral plaque assay, we demonstrated that the presence of the SARS-CoV-2 RBD in the VSV-Δ51 genome is associated with a significantly larger viral plaque surface area and significantly higher virus titers. Subsequently, using an ATP release-based assay, we demonstrated that the SARS-CoV-2 RBD could enhance VSV-Δ51 oncolytic activity in vitro. This observation was further supported using the B16F10 tumor model. These findings highlighted a novel use of the SARS-CoV-2 RBD as an anticancer agent.Instituto de BiotecnologíaFil: Alkayyal, Almohanad A. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia SauditaFil: Alkayyal, Almohanad A. King Abdullah International Medical Research Center. Immunology Research Program; Arabia SauditaFil: Ajina, Reham. King Abdullah International Medical Research Center. Immunology Research Program; Arabia SauditaFil: Ajina, Reham. King Saud bin Abdulaziz University for Health Sciences. College of Applied Medical Sciences. Department of Clinical Laboratory Sciences; Arabia SauditaFil: Cacciabue, Marco Polo Domingo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Cacciabue, Marco Polo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cacciabue, Marco Polo Domingo. Universidad Nacional de Luján. Departamento de Ciencias Básicas; ArgentinaFil: Alkayyal, Aaesha A. Taibah University. College of Medicine; Arabia SauditaFil: Saeedi, Nizar H. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia SauditaFil: Hussain Alshehry, Taofik. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia SauditaFil: Kaboha, Feras. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia SauditaFil: Alotaibi, Mohammed A. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia SauditaFil: Alotaibi, Mohammed A. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia SauditaFil: Zaidan, Nada. King Abdulaziz City for Science and Technology. Joint Centers of Excellence Program. 8King Abdulaziz City for Science and Technology-Brigham and Women's Hospital (KACST-BWH) Centre of Excellence for Biomedicine; Arabia SauditaFil: Shah, Khalid. Harvard Medical School. Brigham and Women’s Hospital. Center for Stem Cell and Translational Immunotherapy (CSTI); Estados UnidosFil: Shah, Khalid. Harvard Medical School. Brigham and Women’s Hospital. Department of Neurosurgery; Estados UnidosFil: Shah, Khalid. Harvard University. Harvard Stem Cell Institute; Estados UnidosFil: Alroqi, Fayhan. King Abdullah International Medical Research Center. Immunology Research Program; Arabia SauditaFil: Alroqi, Fayhan. Ministry of the National Guard. Department of Immunology; Arabia SauditaFil: Alroqi, Fayhan. King Saud bin Abdulaziz University for Health Sciences. Faculty of Medicine; Arabia SauditaFil: Bakur Mahmoud, Ahmad. Taibah University. College of Applied Medical Sciences; Arabia SauditaFil: Bakur Mahmoud, Ahmad. Taibah University. Strategic Research and Innovation Laboratories; Arabia SauditaFil: Bakur Mahmoud, Ahmad. King Abdullah International Medical Research Center. Immunology Research Program; Arabia SauditaFrontiers Media2023-09-15T10:32:33Z2023-09-15T10:32:33Z2023-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/15220https://www.frontiersin.org/articles/10.3389/fimmu.2023.1082191/full1664-3224https://doi.org/10.3389/fimmu.2023.1082191Frontiers in Immunology 14 : 1082191 (Enero 2023)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-29T13:46:06Zoai:localhost:20.500.12123/15220instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-29 13:46:06.524INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
title SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
spellingShingle SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
Alkayyal, Almohanad A.
Severe Acute Respiratory Syndrome Coronavirus 2
Oncology
Melanoma
Vesicular Stomatitis Virus
Coronavirus del Síndrome Respiratorio Agudo Arave 2
Oncología
Virus de la Estomatitis Vesicular
SARS-CoV-2
Viroterapia
Agente Anticancerígeno
Virotherapy
Anticancer Agent
title_short SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
title_full SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
title_fullStr SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
title_full_unstemmed SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
title_sort SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
dc.creator.none.fl_str_mv Alkayyal, Almohanad A.
Ajina, Reham
Cacciabue, Marco Polo Domingo
Alkayyal, Aaesha A.
Saeedi, Nizar H.
Hussain Alshehry, Taofik
Kaboha, Feras
Alotaibi, Mohammed A.
Zaidan, Nada
Shah, Khalid
Alroqi, Fayhan
Bakur Mahmoud, Ahmad
author Alkayyal, Almohanad A.
author_facet Alkayyal, Almohanad A.
Ajina, Reham
Cacciabue, Marco Polo Domingo
Alkayyal, Aaesha A.
Saeedi, Nizar H.
Hussain Alshehry, Taofik
Kaboha, Feras
Alotaibi, Mohammed A.
Zaidan, Nada
Shah, Khalid
Alroqi, Fayhan
Bakur Mahmoud, Ahmad
author_role author
author2 Ajina, Reham
Cacciabue, Marco Polo Domingo
Alkayyal, Aaesha A.
Saeedi, Nizar H.
Hussain Alshehry, Taofik
Kaboha, Feras
Alotaibi, Mohammed A.
Zaidan, Nada
Shah, Khalid
Alroqi, Fayhan
Bakur Mahmoud, Ahmad
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Severe Acute Respiratory Syndrome Coronavirus 2
Oncology
Melanoma
Vesicular Stomatitis Virus
Coronavirus del Síndrome Respiratorio Agudo Arave 2
Oncología
Virus de la Estomatitis Vesicular
SARS-CoV-2
Viroterapia
Agente Anticancerígeno
Virotherapy
Anticancer Agent
topic Severe Acute Respiratory Syndrome Coronavirus 2
Oncology
Melanoma
Vesicular Stomatitis Virus
Coronavirus del Síndrome Respiratorio Agudo Arave 2
Oncología
Virus de la Estomatitis Vesicular
SARS-CoV-2
Viroterapia
Agente Anticancerígeno
Virotherapy
Anticancer Agent
dc.description.none.fl_txt_mv Despite recent advances in the research on oncolytic viruses (OVs), a better understanding of how to enhance their replication is key to improving their therapeutic index. Understanding viral replication is important to improve treatment outcomes based on enhanced viral spreading within the tumor milieu. The VSV-Δ51 oncolytic virus has been widely used as an anticancer agent with a high selectivity profile. In this study, we examined the role of the SARS-CoV-2 spike protein receptor-binding domain (RBD) in enhancing VSV-Δ51 viral production and oncolytic activity. To test this hypothesis, we first generated a novel VSV-Δ51 mutant that encoded the SARS-COV-2 RBD and compared viral spreading and viral yield between VSV-Δ51-RBD and VSV-Δ51 in vitro. Using the viral plaque assay, we demonstrated that the presence of the SARS-CoV-2 RBD in the VSV-Δ51 genome is associated with a significantly larger viral plaque surface area and significantly higher virus titers. Subsequently, using an ATP release-based assay, we demonstrated that the SARS-CoV-2 RBD could enhance VSV-Δ51 oncolytic activity in vitro. This observation was further supported using the B16F10 tumor model. These findings highlighted a novel use of the SARS-CoV-2 RBD as an anticancer agent.
Instituto de Biotecnología
Fil: Alkayyal, Almohanad A. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia Saudita
Fil: Alkayyal, Almohanad A. King Abdullah International Medical Research Center. Immunology Research Program; Arabia Saudita
Fil: Ajina, Reham. King Abdullah International Medical Research Center. Immunology Research Program; Arabia Saudita
Fil: Ajina, Reham. King Saud bin Abdulaziz University for Health Sciences. College of Applied Medical Sciences. Department of Clinical Laboratory Sciences; Arabia Saudita
Fil: Cacciabue, Marco Polo Domingo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Cacciabue, Marco Polo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cacciabue, Marco Polo Domingo. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentina
Fil: Alkayyal, Aaesha A. Taibah University. College of Medicine; Arabia Saudita
Fil: Saeedi, Nizar H. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia Saudita
Fil: Hussain Alshehry, Taofik. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia Saudita
Fil: Kaboha, Feras. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia Saudita
Fil: Alotaibi, Mohammed A. University of Tabuk. Faculty of Applied Medical Sciences. Department of Medical Laboratory Technology; Arabia Saudita
Fil: Alotaibi, Mohammed A. Ministry of National Guard Health Affairs. King Saud University for Health Sciences. King Abdullah International Medical Research Centre; Arabia Saudita
Fil: Zaidan, Nada. King Abdulaziz City for Science and Technology. Joint Centers of Excellence Program. 8King Abdulaziz City for Science and Technology-Brigham and Women's Hospital (KACST-BWH) Centre of Excellence for Biomedicine; Arabia Saudita
Fil: Shah, Khalid. Harvard Medical School. Brigham and Women’s Hospital. Center for Stem Cell and Translational Immunotherapy (CSTI); Estados Unidos
Fil: Shah, Khalid. Harvard Medical School. Brigham and Women’s Hospital. Department of Neurosurgery; Estados Unidos
Fil: Shah, Khalid. Harvard University. Harvard Stem Cell Institute; Estados Unidos
Fil: Alroqi, Fayhan. King Abdullah International Medical Research Center. Immunology Research Program; Arabia Saudita
Fil: Alroqi, Fayhan. Ministry of the National Guard. Department of Immunology; Arabia Saudita
Fil: Alroqi, Fayhan. King Saud bin Abdulaziz University for Health Sciences. Faculty of Medicine; Arabia Saudita
Fil: Bakur Mahmoud, Ahmad. Taibah University. College of Applied Medical Sciences; Arabia Saudita
Fil: Bakur Mahmoud, Ahmad. Taibah University. Strategic Research and Innovation Laboratories; Arabia Saudita
Fil: Bakur Mahmoud, Ahmad. King Abdullah International Medical Research Center. Immunology Research Program; Arabia Saudita
description Despite recent advances in the research on oncolytic viruses (OVs), a better understanding of how to enhance their replication is key to improving their therapeutic index. Understanding viral replication is important to improve treatment outcomes based on enhanced viral spreading within the tumor milieu. The VSV-Δ51 oncolytic virus has been widely used as an anticancer agent with a high selectivity profile. In this study, we examined the role of the SARS-CoV-2 spike protein receptor-binding domain (RBD) in enhancing VSV-Δ51 viral production and oncolytic activity. To test this hypothesis, we first generated a novel VSV-Δ51 mutant that encoded the SARS-COV-2 RBD and compared viral spreading and viral yield between VSV-Δ51-RBD and VSV-Δ51 in vitro. Using the viral plaque assay, we demonstrated that the presence of the SARS-CoV-2 RBD in the VSV-Δ51 genome is associated with a significantly larger viral plaque surface area and significantly higher virus titers. Subsequently, using an ATP release-based assay, we demonstrated that the SARS-CoV-2 RBD could enhance VSV-Δ51 oncolytic activity in vitro. This observation was further supported using the B16F10 tumor model. These findings highlighted a novel use of the SARS-CoV-2 RBD as an anticancer agent.
publishDate 2023
dc.date.none.fl_str_mv 2023-09-15T10:32:33Z
2023-09-15T10:32:33Z
2023-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/15220
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1082191/full
1664-3224
https://doi.org/10.3389/fimmu.2023.1082191
url http://hdl.handle.net/20.500.12123/15220
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1082191/full
https://doi.org/10.3389/fimmu.2023.1082191
identifier_str_mv 1664-3224
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rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Frontiers in Immunology 14 : 1082191 (Enero 2023)
reponame:INTA Digital (INTA)
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