Virus contaminations of cell cultures – A biotechnological view
Open accessAbstract
In contrast to contamination by microbes and mycoplasma, which can be relatively easily detected, viral contamination present a serious threat because of the difficulty in detecting some viruses and the lack of effective methods of treating infected cell cultures. While some viruses are capable of causing morphological changes to infected cells (e.g. cytopathic effect) which are detectable by microscopy some viral contaminations result in the integration of the viral genome as provirus, this causes no visual evidence, by means of modification of the cellular morphology. Virus production from such cell lines, are potentially dangerous for other cell cultures (in research labs)by cross contaminations, or for operators and patients (in the case of the production of injectable biologicals) because of potential infection. The only way to keep cell cultures for research, development, and the biotech industry virus-free is the prevention of such contaminations. Cell cultures can become contaminated by the following means: firstly, they may already be contaminated as primary cultures (because the source of the cells was already infected), secondly, they were contaminated due to the use of contaminated raw materials, or thirdly, they were contaminated via an animal passage. This overview describes the problems and risks associated with viral contaminations in animal cell culture, describes the origins of these contaminations as well as the most important virsuses associated with viral contaminations in cell culture. In addition, ways to prevent viral contaminations as well as measures undertaken to avoid and assess risks for viral contaminations as performed in the biotech industry are briefly described.
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Animal-derived raw materials, especially serum, carry a relatively higher risk of being contaminated with virus and are thus being replaced where possible throughout the industry.
“Animal-derived raw materials (ADRMs), especially serum, carry a relatively higher risk of being contaminated with virus and are thus being replaced where possible throughout the industry 1,9,13 .”
From Viral contamination in biologic manufacture and implications for emerging therapies (2020) · cites this paper as [1]
The paper's introductory overview identifies contaminated raw materials as a route by which cell cultures acquire viruses, and its references include reports of viral contamination in calf serum. The passages retrieved do not establish that animal-derived materials pose a relatively higher risk than alternatives or that they are being replaced throughout the industry. (LLM, conf=0.73)
Experimental — accuracy not yet measuredIn the 20th century, several vaccine products were unintentionally contaminated with unwanted viruses during their production.
“In the 20 th century several vaccine products were unintentionally contaminated with unwanted viruses during their production [1][2][3] .”
From Viral contamination in biologic manufacture and implications for emerging therapies (2020) · cites this paper as [1]
Viruses are of particular concern as contaminants because they are often more difficult to detect than other microbial contaminants.
“Viruses are of particular concern as they are often more difficult to detect than other microbial contaminants 1 .”
From Viral contamination in biologic manufacture and implications for emerging therapies (2020) · cites this paper as [1]
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Cites
HUMAN EXPOSURE TO SV40: REVIEW AND COMMENT12
SHAH, K., & NATHANSON, N. (1976) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a112197 · Cited by 339 · see citing works
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Coecke, S., Balls, M., Bowe, G., Davis, J., Gstraunthaler, G., Hartung, T., Hay, R., Merten, O.-W., Price, A., Schechtman, L., et al. (2005) · Alternatives to Laboratory Animals · doi:10.1177/026119290503300313 · Cited by 371 · see citing works
Self-citationViral contamination in biologic manufacture and implications for emerging therapies
Barone, P. W., Wiebe, M. E., Leung, J. C., Hussein, I. T. M., Keumurian, F. J., Bouressa, J., Brussel, A., Chen, D., Chong, M., Dehghani, H., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0507-2 · Cited by 212 · see citing works
A Beginner’s Guide to Cell Culture: Practical Advice for Preventing Needless Problems
Weiskirchen, S., Schröder, S. K., Buhl, E. M., & Weiskirchen, R. (2023) · Cells · doi:10.3390/cells12050682 · Cited by 148 · see citing works
- Authors
- Merten, O.-W.
- Affiliations
- Genethon (France) (FR)
- Corresponding author
- Merten, O.-W.
- ORCID
- Merten, O.-W.
- Venue
- Cytotechnology
- Published
- 2002-06
- Volume
- 39
- Issue
- 2
- Pages
- 91-116
- ISSN
- 0920-9069 (ISSN-L)
- 1573-0778
- PMC
- PMC3463984
- OpenAlex
- W2153805979
- Cited by
- 133
- References
- 1
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 13 · 2021: 12 · 2020: 14 · 2019: 10 · 2018: 7 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 9 · 2013: 5
- FWCI
- 0.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cytotechnology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- viral contamination, cell culture contamination, animal cell culture, provirus integration, cytopathic effect, cross-contamination, animal passage, contamination prevention, risk assessment, biotechnology industry
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