ArticleBMC biology2021
Cell culture-based production and in vivo characterization of purely clonal defective interfering influenza virus particles.
Article in BMC biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Meta-analysis of genomic characteristics for antiviral influenza defective interfering particle prioritization.NAR genomics and bioinformatics · 2025Pooled it
- Pooled it
- Hybrid therapeutic agents for self-oxygenating wound therapy via infectious microenvironment modulation.iScience · 2025Article
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- Identification, functional analysis, and clinical applications of defective viral genomes.Frontiers in microbiology · 2025Review
- Antivirotics based on defective interfering particles: emerging concepts and challenges.Frontiers in cellular and infection microbiology · 2025Review
- Innovations in cell culture-based influenza vaccine manufacturing - from static cultures to high cell density cultivations.Human vaccines & immunotherapeutics · 2024Review
- Production of antiviral "OP7 chimera" defective interfering particles free of infectious virus.Applied microbiology and biotechnology · 2024Article
- Review
- Mathematical model calibrated toiScience · 2024Article
- Differential lung gene expression changes in C57BL/6 and DBA/2 mice carrying an identical functional Mx1 gene reveals crucial differences in the host response.BMC genomic data · 2024Article
- Generation of "OP7 chimera" defective interfering influenza A particle preparations free of infectious virus that show antiviral efficacy in mice.Scientific reports · 2023Article
- Article
- An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animals.iScience · 2023Article
- Semi-continuous Propagation of Influenza A Virus and Its Defective Interfering Particles: Analyzing the Dynamic Competition To Select Candidates for Antiviral Therapy.Journal of virology · 2021Article
- Cell culture-based production of defective interfering influenza A virus particles in perfusion mode using an alternating tangential flow filtration system.Applied microbiology and biotechnology · 2021Article
- Multiscale model of defective interfering particle replication for influenza A virus infection in animal cell culture.PLoS computational biology · 2021Article
- Article
- In Vitro Antiviral Activity of Green Tea Polyphenon-60 against Avian Paramyxoviruses.Veterinary medicine international · 2021Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundInfections with influenza A virus (IAV) cause high morbidity and mortality in humans. Additional to vaccination, antiviral drugs are a treatment option. Besides FDA-approved drugs such as oseltamivir or zanamivir, virus-derived defective interfering (DI) particles (DIPs) are considered promising new agents. IAV DIPs typically contain a large internal deletion in one of their eight genomic viral RNA (vRNA) segments. Consequently, DIPs miss the genetic information necessary for replication and can usually only propagate by co-infection with infectious standard virus (STV), compensating for their defect. In such a co-infection scenario, DIPs interfere with and suppress STV replication, which constitutes their antiviral potential.
resultsIn the present study, we generated a genetically engineered MDCK suspension cell line for production of a purely clonal DIP preparation that has a large deletion in its segment 1 (DI244) and is not contaminated with infectious STV as egg-derived material. First, the impact of the multiplicity of DIP (MODIP) per cell on DI244 yield was investigated in batch cultivations in shake flasks. Here, the highest interfering efficacy was observed for material produced at a MODIP of 1E-2 using an in vitro interference assay. Results of RT-PCR suggested that DI244 material produced was hardly contaminated with other defective particles. Next, the process was successfully transferred to a stirred tank bioreactor (500 mL working volume) with a yield of 6.0E+8 PFU/mL determined in genetically modified adherent MDCK cells. The produced material was purified and concentrated about 40-fold by membrane-based steric exclusion chromatography (SXC). The DI244 yield was 92.3% with a host cell DNA clearance of 97.1% (99.95% with nuclease digestion prior to SXC) and a total protein reduction of 97.2%. Finally, the DIP material was tested in animal experiments in D2(B6).A2G-Mx1
conclusionIn summary, experiments not only demonstrated that purely clonal influenza virus DIP preparations can be obtained with high titers from animal cell cultures but confirmed the potential of cell culture-derived DIPs as an antiviral agent.
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