Contamination of Genetically Engineered CHO-cells by Epizootic Haemorrhagic Disease Virus (EHDV)
Abstract
The characterization of a contaminating virus which was detected in genetically-engineered Chinese hamster ovary (CHO) cells during the production of biologicals is described in the present paper. Under electron microscopy, the contaminating virus had a morphology resembling that of an orbivirus. The relationship was confirmed by nucleic acid analysis which showed a RNA segment pattern characteristic of orbiviruses. With an immunoperoxidase staining of monolayer cells and through sero-neutralization tests the virus was identified as being identical to Epizootic Haemorrhagic Disease Virus (EHDV), isolate 318 (untyped) from Bahrain. Potential sources of the contaminating virus and feasible procedures to avoid adventitous virus infections in cell cultures are discussed.
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The authors are aware of only 26 virus contaminations over the past 36 years, 18 of which were reported directly as part of this study.
“These events are rare; we are aware of only 26 virus contaminations over the past 36 years (Table 1) [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] , 18 of which were reported directly as a part of this study.”
From Viral contamination in biologic manufacture and implications for emerging therapies (2020) · cites this paper as [19]
In all reported cases of CHO cell-derived bulk harvest contamination, raw materials used in production were suspected as the source of viral contamination.
“In all of these reported cases, raw materials used in production were suspected as the source of viral contamination (Garnick, 1998;Rabenau et al., 1993;Onions, 2004).”
From Virus susceptibility of Chinese hamster ovary (CHO) cells and detection of viral contaminations by adventitious agent testing (2010) · cites this paper as Rabenau et al., 1993
Only a few documented historical contaminations of CHO cells have occurred.
“For CHO cells, despite their wide use in various biotechnology applications, only a few documented historical contaminations have occurred (Garnick, 1996;Nims, 2006;Rabenau et al., 1993), which strengthens the argument of inherently high safety margins associated with the use of this cell line.”
From Virus susceptibility of Chinese hamster ovary (CHO) cells and detection of viral contaminations by adventitious agent testing (2010) · cites this paper as Rabenau et al., 1993
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Viral 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
Berting, A., Farcet, M. R., & Kreil, T. R. (2010) · Biotechnology and Bioengineering · doi:10.1002/bit.22723 · Cited by 88 · see citing works
“In the case of CVV and more so VSV, the ability to reproduce on CHO cells appeared to improve after the first 7 1 days incubation, possibly indicating an adaption of the virus to growth in CHO cells, as higher titers were detected more consistently in the 14d CHO cell culture supernatant (Fig.”
BackgroundMethodInfluentialQiu, Y., Jones, N., Busch, M., Pan, P., Keegan, J., Zhou, W., Plavsic, M., Hayes, M., McPherson, J. M., Edmunds, T., et al. (2013) · Biotechnology and Bioengineering · doi:10.1002/bit.24791 · Cited by 29 · see citing works
Conley, M., Emmott, E., Orton, R., Taylor, D., Carneiro, D. G., Murata, K., Goodfellow, I. G., Hansman, G. S., & Bhella, D. (2017) · Journal of General Virology · doi:10.1099/jgv.0.000658 · Cited by 8 · see citing works
- Authors
- Rabenau, H., Ohlinger, V., Anderson, J., Selb, B., Cinatl, J., Wolf, W., Frost, J., Mellor, P., & Doerr, H. W.
- Affiliations
- The Pirbright Institute (GB)
- Venue
- Biologicals
- Publisher
- Elsevier BV
- Published
- 1993-09
- Volume
- 21
- Issue
- 3
- Pages
- 207-214
- ISSN
- 1045-1056 (ISSN-L)
- OpenAlex
- W2058967378
- Cited by
- 68
- References
- 0
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 5
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biologicals (publishedVersion)
- PubMed (publishedVersion)
- OpenAgrar (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Vector-Borne Animal Diseases
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- epizootic hemorrhagic disease virus, CHO cells, genetically engineered cell lines, Orbivirus, immunoperoxidase staining, seroneutralization
- MeSH terms
- Animals, Cells, Cultured, Cytopathogenic Effect, Viral, Genetic Engineering, Cricetinae, Humans, Immunoenzyme Techniques, Microscopy, Electron, Neutralization Tests, Tumor Cells, Cultured, CHO Cells, Hemorrhagic Disease Virus, Epizootic
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