Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.

Influenza viruses are a major public health burden during seasonal epidemics and a continuous threat due to their potential to cause pandemics. Annual vaccination provides the best protection against the contagious respiratory illness caused by influenza viruses. However, the current production capa...

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Autores principales:	Timo Frensing, Frank Stefan Heldt, Antje Pflugmacher, Ilona Behrendt, Ingo Jordan, Dietrich Flockerzi, Yvonne Genzel, Udo Reichl
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e43c0da3a1f34fad8e115fab50095f7d
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spelling	oai:doaj.org-article:e43c0da3a1f34fad8e115fab50095f7d2021-11-18T08:56:47ZContinuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.1932-620310.1371/journal.pone.0072288https://doaj.org/article/e43c0da3a1f34fad8e115fab50095f7d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24039749/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Influenza viruses are a major public health burden during seasonal epidemics and a continuous threat due to their potential to cause pandemics. Annual vaccination provides the best protection against the contagious respiratory illness caused by influenza viruses. However, the current production capacities for influenza vaccines are insufficient to meet the increasing demands. We explored the possibility to establish a continuous production process for influenza viruses using the duck-derived suspension cell line AGE1.CR. A two-stage bioreactor setup was designed in which cells were cultivated in a first stirred tank reactor where an almost constant cell concentration was maintained. Cells were then constantly fed to a second bioreactor where virus infection and replication took place. Using this two-stage reactor system, it was possible to continuously produce influenza viruses. Surprisingly, virus titers showed a periodic increase and decrease during the run-time of 17 days. These titer fluctuations were caused by the presence of defective interfering particles (DIPs), which we detected by PCR. Mathematical modeling confirmed this observation showing that constant virus titers can only emerge in the absence of DIPs. Even with very low amounts of DIPs in the seed virus and very low rates for de novo DIP generation, defective viruses rapidly accumulate and, therefore, represent a serious challenge for continuous vaccine production. Yet, the continuous replication of influenza virus using a two-stage bioreactor setup is a novel tool to study aspects of viral evolution and the impact of DIPs.Timo FrensingFrank Stefan HeldtAntje PflugmacherIlona BehrendtIngo JordanDietrich FlockerziYvonne GenzelUdo ReichlPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e72288 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Timo Frensing Frank Stefan Heldt Antje Pflugmacher Ilona Behrendt Ingo Jordan Dietrich Flockerzi Yvonne Genzel Udo Reichl Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.
description	Influenza viruses are a major public health burden during seasonal epidemics and a continuous threat due to their potential to cause pandemics. Annual vaccination provides the best protection against the contagious respiratory illness caused by influenza viruses. However, the current production capacities for influenza vaccines are insufficient to meet the increasing demands. We explored the possibility to establish a continuous production process for influenza viruses using the duck-derived suspension cell line AGE1.CR. A two-stage bioreactor setup was designed in which cells were cultivated in a first stirred tank reactor where an almost constant cell concentration was maintained. Cells were then constantly fed to a second bioreactor where virus infection and replication took place. Using this two-stage reactor system, it was possible to continuously produce influenza viruses. Surprisingly, virus titers showed a periodic increase and decrease during the run-time of 17 days. These titer fluctuations were caused by the presence of defective interfering particles (DIPs), which we detected by PCR. Mathematical modeling confirmed this observation showing that constant virus titers can only emerge in the absence of DIPs. Even with very low amounts of DIPs in the seed virus and very low rates for de novo DIP generation, defective viruses rapidly accumulate and, therefore, represent a serious challenge for continuous vaccine production. Yet, the continuous replication of influenza virus using a two-stage bioreactor setup is a novel tool to study aspects of viral evolution and the impact of DIPs.
format	article
author	Timo Frensing Frank Stefan Heldt Antje Pflugmacher Ilona Behrendt Ingo Jordan Dietrich Flockerzi Yvonne Genzel Udo Reichl
author_facet	Timo Frensing Frank Stefan Heldt Antje Pflugmacher Ilona Behrendt Ingo Jordan Dietrich Flockerzi Yvonne Genzel Udo Reichl
author_sort	Timo Frensing
title	Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.
title_short	Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.
title_full	Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.
title_fullStr	Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.
title_full_unstemmed	Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.
title_sort	continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e43c0da3a1f34fad8e115fab50095f7d
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Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles.

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