Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission

Abstract:

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.

SEEK ID: https://fairdomhub.org/publications/520

DOI: 10.1038/s41598-018-33487-8

Projects: COVID-19 Disease Map

Publication type: Journal

Journal: Scientific Reports

Citation: Sci Rep 8(1),15177

Date Published: 1st Dec 2018

URL: https://www.nature.com/articles/s41598-018-33487-8

Registered Mode: imported from a bibtex file

Authors: Doreen Muth, Victor Max Corman, Hanna Roth, Tabea Binger, Ronald Dijkman, Lina Theresa Gottula, Florian Gloza-Rausch, Andrea Balboni, Mara Battilani, Danijela Rihtarič, Ivan Toplak, Ramón Seage Ameneiros, Alexander Pfeifer, Volker Thiel, Jan Felix Drexler, Marcel Alexander Müller, Christian Drosten

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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. In Scientific Reports (Vol. 8, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1038/s41598-018-33487-8
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Created: 8th Apr 2020 at 20:14

Last updated: 8th Dec 2022 at 17:26

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