About: Production of Defective Interfering Particles of Influenza A Virus in Parallel Continuous Cultures at Two Residence Times—Insights From qPCR Measurements and Viral Dynamics Modeling

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About: Production of Defective Interfering Particles of Influenza A Virus in Parallel Continuous Cultures at Two Residence Times—Insights From qPCR Measurements and Viral Dynamics Modeling Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Production of Defective Interfering Particles of Influenza A Virus in Parallel Continuous Cultures at Two Residence Times—Insights From qPCR Measurements and Viral Dynamics Modeling
Creator	Genzel, Yvonne Laske, Tanja Rammhold, Markus Reichl, Udo Tapia, Felipe Herwig, Christoph Ma, Wasik Mao, Xiangzhao Wasik, Milena
Source	Medline; PMC
abstract	Defective interfering particles (DIPs) are a natural byproduct of influenza A virus (IAV) replication. DIPs interfere with the propagation and spread of infectious standard virus (STV), reduce virus yields by competing for viral and cellular resources, and induce antiviral responses. These properties open exciting possibilities for the development of DIP-based antivirals. Exploring options for cell culture-based DIP production, we have established a fully continuous cultivation process, where one bioreactor is used to grow cells that are fed to two bioreactors operated in parallel for virus production. This system allows head-to-head comparisons of STV and DIP replication dynamics over extended time periods. Cultivations were performed at two residence times (RT, 22 and 36 h) using MDCK suspension cells grown in a fully defined medium. For infection, we used a virus seed generated by reverse genetics containing STVs and a known DIP carrying a deletion in segment 1 (delS1(1)). Four days post infection, DIPs achieved maximum concentrations of 7.0·10(9) virions/mL and 8.4·10(9) virions/mL for RTs of 22 and 36 h, respectively. Furthermore, oscillations in virus titers with two to three maxima were found for DIP accumulation at 36 and 22 h RT, respectively. To complement the study, a basic mathematical model using simple kinetics and a reasonable number of parameters to describe DIP-propagation in continuous cultures was established. Upon fitting the model individually to each of the two data sets, oscillations in the viral dynamics and the cell population dynamics were described well. Modeling suggests that both STV inactivation and virus degradation have to be taken into account to achieve good agreement of simulations and experimental data for longer RTs. Together, the high DIP titers obtained, and the successful simulation of the experimental data showed that the combination of continuous bioreactors and mathematical models can enable studies regarding DIP dynamics over extended time periods and allow large scale manufacturing of DIP-based antivirals.
has issue date	2019-10-18(xsd:dateTime)
bibo:doi	10.3389/fbioe.2019.00275
bibo:pmid	31681751
has license	cc-by
sha1sum (hex)	198bdc284caeafc6bbff6f925f36eec10d3d033c
schema:url	https://doi.org/10.3389/fbioe.2019.00275
resource representing a document's title	Production of Defective Interfering Particles of Influenza A Virus in Parallel Continuous Cultures at Two Residence Times—Insights From qPCR Measurements and Viral Dynamics Modeling
has PubMed Central identifier	PMC6813217
has PubMed identifier	31681751
schema:publication	Front Bioeng Biotechnol
resource representing a document's body	covid:198bdc284caeafc6bbff6f925f36eec10d3d033c#body_text
is schema:about of	named entity 'INFLUENZA A VIRUS' named entity 'INSIGHTS' named entity 'INFECTION' named entity 'EXPLORING' named entity 'TIMES' named entity 'NUMBER OF' named entity 'MODELING' named entity 'DATA SETS' named entity 'PROPERTIES' named entity 'DYNAMICS' named entity 'ALLOW' named entity 'PROCESS' named entity 'PRODUCTION' named entity 'CELLULAR' covid:arg/198bdc284caeafc6bbff6f925f36eec10d3d033c named entity 'BASIC' named entity 'USED' named entity 'SIMULATIONS' named entity 'POST' named entity 'OSCILLATIONS' named entity 'GOOD' named entity 'PARAMETERS' named entity 'VIRAL AND' named entity 'EXTENDED' named entity 'CONTINUOUS CULTURES' named entity 'INFECTIOUS' named entity 'DELETION' named entity '8.4' named entity 'MAXIMUM' named entity 'PRODUCTION' named entity 'CONTINUOUS CULTURES' named entity 'MODELING' named entity 'FED' named entity 'STANDARD' named entity 'RTS' named entity 'SYSTEM' named entity 'OBTAINED' named entity 'VIRUS PRODUCTION' named entity 'DAYS' named entity 'CITATION' named entity 'QPCR' named entity 'PARALLEL' named entity 'DEFECTIVE INTERFERING PARTICLES' named entity 'STUDY' named entity 'USING' named entity 'PERFORMED' named entity 'MAXIMA' named entity 'PARALLEL' named entity 'DEVELOPMENT' named entity 'ALLOWS' named entity 'FOUND' named entity 'SEED' named entity 'TIME PERIODS' named entity 'SUSPENSION' named entity 'INACTIVATION' named entity 'DIP' named entity 'SEGMENT' named entity 'CULTIVATION' named entity 'NATURAL' named entity 'FULLY' named entity 'DEFECTIVE INTERFERING PARTICLES' named entity 'ACCOUNT' named entity 'TAKEN' named entity 'WHERE' named entity 'AGREEMENT' named entity 'SIMULATION' named entity 'SPREAD' named entity 'BASED' named entity 'DEGRADATION' named entity 'SIMPLE' named entity 'FITTING' named entity 'PROPAGATION' named entity 'MANUFACTURING'

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