Identification and quantitation of vesivirus 2117 particles in bioreactor fluids from infected Chinese hamster ovary cell cultures
Abstract
The prevention of adventitious agent contamination is a top priority throughout the entire biopharmaceutical production process. For example, although viral contamination of cell banks or cell cultures is rare, it can result in serious consequences (e.g., shutdown and decontamination of manufacturing facilities). To ensure virus free production, numerous in vivo and in vitro adventitious agent assays and biophysical characterizations such as electron microscopy are conducted on cell banks, raw materials, process materials, and drug substances throughout the manufacturing process. Molecular assays such as PCR and other nucleotide‐based techniques are also routinely used for screening and identification of any viral agents. However, modern techniques in protein identification of complex protein mixtures have not yet been effectively integrated throughout the industry into current viral testing strategies. Here, we report the identification and quantitation of Vesivirus 2117 particles in bioreactor fluid from infected Chinese hamster ovary cell cultures by global protein sequencing using mass spectrometry in combination with multi‐dimensional liquid‐chromatography. Following mass spectrometric data acquisition and rigorous data analysis, six virus specific peptides were identified. These peptides were fragments of two structural proteins, capsid protein pre‐cursor (four unique peptides) and small structural protein (two unique peptides), from the same species: Vesivirus 2117. Using stable heavy isotope‐labeled peptides as internal standards, we also determined the absolute concentration of Vesivirus particles in the bioreactor fluid and the ratio of two capsid proteins (VP1:VP2) in the particles as approximately 9:1. The positive identification of Vesivirus 2117 was subsequently confirmed by RT‐PCR. Biotechnol. Bioeng. 2013; 110: 1342–1353. © 2012 Wiley Periodicals, Inc.
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Vesivirus 2117 contamination of CHO-cell bioreactors at Genzyme caused significant financial losses and delayed drug delivery to patients with Gaucher or Fabry disease.
“Vesivirus 2117 has caused significant financial losses owing to the contamination of bioreactors at Genzyme (Allston Landing and Geel facilities) where CHO cells were used for the production of biopharmaceuticals.”
From Vesivirus 2117 capsids more closely resemble sapovirus and lagovirus particles than other known vesivirus structures (2017) · cites this paper as [17]
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Self-citation
- Authors
- Qiu, Y., Jones, N., Busch, M., Pan, P., Keegan, J., Zhou, W., Plavsic, M., Hayes, M., McPherson, J. M., Edmunds, T., Zhang, K., & Mattaliano, R. J.
- Corresponding author
- Qiu, Yongchang
- Venue
- Biotechnology and Bioengineering
- Publisher
- Wiley
- Published
- 2012-12-25
- Volume
- 110
- Issue
- 5
- Pages
- 1342-1353
- ISSN
- 0006-3592 (ISSN-L)
- 1097-0290
- OpenAlex
- W2038241066
- Cited by
- 29
- References
- 33
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 1
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biotechnology and Bioengineering (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- virus identification, virus quantitation, biopharmaceutical manufacturing, virus inactivation
- MeSH terms
- Amino Acid Sequence, Animals, Biotechnology, Cell Survival, Chromatography, Ion Exchange, Cricetulus, Cricetinae, Molecular Sequence Data, Peptide Fragments, RNA, Viral, Viral Proteins, Virion, Reproducibility of Results, Polymerase Chain Reaction, CHO Cells, Cell Culture Techniques, Bioreactors, Vesivirus, Tandem Mass Spectrometry
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