SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus
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 mi...
| Autores principales: | , , , , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
Frontiers Media
2023
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| Acceso en línea: | 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 |
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| author | 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_browse | Ajina, Reham Alkayyal, Aaesha A. Alkayyal, Almohanad A. Alotaibi, Mohammed A. Alroqi, Fayhan Bakur Mahmoud, Ahmad Cacciabue, Marco Polo Domingo Hussain Alshehry, Taofik Kaboha, Feras Saeedi, Nizar H. Shah, Khalid Zaidan, Nada |
| 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_sort | Alkayyal, Almohanad A. |
| collection | INTA Digital |
| 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. |
| format | Artículo |
| id | INTA15220 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| record_format | dspace |
| spelling | INTA152202023-09-15T10:42:04Z SARS-CoV-2 RBD protein enhances the oncolytic activity of the vesicular stomatitis virus 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 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 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 2023-09-15T10:32:33Z 2023-09-15T10:32:33Z 2023-01 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Frontiers Media Frontiers in Immunology 14 : 1082191 (Enero 2023) |
| spellingShingle | 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 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 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 |
| 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_short | 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 |
| 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 |
| 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 |
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