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OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential

ABSTRACT: The novel influenza A virus (IAV) defective interfering particle “OP7” inhibits IAV replication in a co-infection and was previously suggested as a promising antiviral agent. Here, we report a batch-mode cell culture-based production process for OP7. In the present study, a seed virus cont...

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Autores principales: Hein, Marc D., Kollmus, Heike, Marichal-Gallardo, Pavel, Püttker, Sebastian, Benndorf, Dirk, Genzel, Yvonne, Schughart, Klaus, Kupke, Sascha Y., Reichl, Udo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778630/
https://www.ncbi.nlm.nih.gov/pubmed/33275160
http://dx.doi.org/10.1007/s00253-020-11029-5
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author Hein, Marc D.
Kollmus, Heike
Marichal-Gallardo, Pavel
Püttker, Sebastian
Benndorf, Dirk
Genzel, Yvonne
Schughart, Klaus
Kupke, Sascha Y.
Reichl, Udo
author_facet Hein, Marc D.
Kollmus, Heike
Marichal-Gallardo, Pavel
Püttker, Sebastian
Benndorf, Dirk
Genzel, Yvonne
Schughart, Klaus
Kupke, Sascha Y.
Reichl, Udo
author_sort Hein, Marc D.
collection PubMed
description ABSTRACT: The novel influenza A virus (IAV) defective interfering particle “OP7” inhibits IAV replication in a co-infection and was previously suggested as a promising antiviral agent. Here, we report a batch-mode cell culture-based production process for OP7. In the present study, a seed virus containing standard virus (STV) and OP7 was used. The yield of OP7 strongly depended on the production multiplicity of infection. To inactivate infectious STV in the OP7 material, which may cause harm in a potential application, UV irradiation was used. The efficacy of OP7 in this material was preserved, as shown by an in vitro interference assay. Next, steric exclusion chromatography was used to purify and to concentrate (~ 13-fold) the UV-treated material. Finally, administration of produced OP7 material in mice did not show any toxic effects. Furthermore, all mice infected with a lethal dose of IAV survived the infection upon OP7 co-treatment. Thus, the feasibility of a production workflow for OP7 and its potential for antiviral treatment was demonstrated. KEY POINTS: • OP7 efficacy strongly depended on the multiplicity of infection used for production • Purification by steric exclusion chromatography increased OP7 efficacy • OP7-treated mice were protected against a lethal infection with IAV SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00253-020-11029-5.
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spelling pubmed-77786302021-01-11 OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential Hein, Marc D. Kollmus, Heike Marichal-Gallardo, Pavel Püttker, Sebastian Benndorf, Dirk Genzel, Yvonne Schughart, Klaus Kupke, Sascha Y. Reichl, Udo Appl Microbiol Biotechnol Biotechnological Products and Process Engineering ABSTRACT: The novel influenza A virus (IAV) defective interfering particle “OP7” inhibits IAV replication in a co-infection and was previously suggested as a promising antiviral agent. Here, we report a batch-mode cell culture-based production process for OP7. In the present study, a seed virus containing standard virus (STV) and OP7 was used. The yield of OP7 strongly depended on the production multiplicity of infection. To inactivate infectious STV in the OP7 material, which may cause harm in a potential application, UV irradiation was used. The efficacy of OP7 in this material was preserved, as shown by an in vitro interference assay. Next, steric exclusion chromatography was used to purify and to concentrate (~ 13-fold) the UV-treated material. Finally, administration of produced OP7 material in mice did not show any toxic effects. Furthermore, all mice infected with a lethal dose of IAV survived the infection upon OP7 co-treatment. Thus, the feasibility of a production workflow for OP7 and its potential for antiviral treatment was demonstrated. KEY POINTS: • OP7 efficacy strongly depended on the multiplicity of infection used for production • Purification by steric exclusion chromatography increased OP7 efficacy • OP7-treated mice were protected against a lethal infection with IAV SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00253-020-11029-5. Springer Berlin Heidelberg 2020-12-04 2021 /pmc/articles/PMC7778630/ /pubmed/33275160 http://dx.doi.org/10.1007/s00253-020-11029-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Biotechnological Products and Process Engineering
Hein, Marc D.
Kollmus, Heike
Marichal-Gallardo, Pavel
Püttker, Sebastian
Benndorf, Dirk
Genzel, Yvonne
Schughart, Klaus
Kupke, Sascha Y.
Reichl, Udo
OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential
title OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential
title_full OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential
title_fullStr OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential
title_full_unstemmed OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential
title_short OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential
title_sort op7, a novel influenza a virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential
topic Biotechnological Products and Process Engineering
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778630/
https://www.ncbi.nlm.nih.gov/pubmed/33275160
http://dx.doi.org/10.1007/s00253-020-11029-5
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