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Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission
Open accessAbstract
A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (−29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.
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Self-citationGassen, N. C., Niemeyer, D., Muth, D., Corman, V. M., Martinelli, S., Gassen, A., Hafner, K., Papies, J., Mösbauer, K., Zellner, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13659-4 · Cited by 356
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Metadata
- Authors
- Muth, D., Corman, V. M., Roth, H., Binger, T., Dijkman, R., Gottula, L. T., Gloza-Rausch, F., Balboni, A., Battilani, M., Rihtarič, D., Toplak, I., Ameneiros, R. S., Pfeifer, A., Thiel, V., Drexler, J. F., Müller, M. A., & Drosten, C.
- Venue
- Scientific Reports
- Published
- 2018-10-11
- Volume
- 8
- Issue
- 1
- Pages
- 15177-15177
- ISSN
- 2045-2322 (ISSN-L)
- OpenAlex
- W2894950287
- Cited by
- 197
- References
- 5
- FWCI
- 24.03
- Type
- journal article
- Language
- en
- Open access
- gold
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- Muth, D., Corman, V. M., Roth, H., Binger, T., Dijkman, R., Gottula, L. T., Gloza-Rausch, F., Balboni, A., Battilani, M., Rihtarič, D., Toplak, I., Ameneiros, R. S., Pfeifer, A., Thiel, V., Drexler, J. F., Müller, M. A., & Drosten, C. (2018). Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission. Scientific Reports. https://doi.org/10.1038/s41598-018-33487-8
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
