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.

Details

Title
Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission
Author
Muth, Doreen 1 ; Corman, Victor Max 1   VIAFID ORCID Logo  ; Roth, Hanna 2 ; Binger, Tabea 2 ; Dijkman, Ronald 3   VIAFID ORCID Logo  ; Gottula, Lina Theresa 1 ; Gloza-Rausch, Florian 4 ; Balboni, Andrea 5   VIAFID ORCID Logo  ; Battilani, Mara 5 ; Rihtarič, Danijela 6 ; Toplak, Ivan 6 ; Ramón Seage Ameneiros 7 ; Pfeifer, Alexander 8 ; Thiel, Volker 3 ; Jan Felix Drexler 1 ; Müller, Marcel Alexander 1   VIAFID ORCID Logo  ; Drosten, Christian 1 

1  Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Center for Infection Research (DZIF), Berlin, Germany; Institute of Virology, University of Bonn Medical Centre, Bonn, Germany 
2  Institute of Virology, University of Bonn Medical Centre, Bonn, Germany 
3  Federal Department of Home Affairs, Institute of Virology and Immunology IVI, Bern and Mittelhäusern, Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland 
4  Noctalis, Centre for Bat Protection and Information, Bad Segeberg, Germany 
5  Dipartimento di Scienze Mediche Veterinarie, Facoltà di Medicina Veterinaria, Alma Mater Studiorum-Università di Bologna, Ozzano Emilia, (BO), Italy 
6  Virology Unit, Institute of Microbiology and Parasitology, Veterinary Faculty, University of Ljubljana, Ljubljana, Slovenia 
7  Institute of Evolutionary Ecology and Conservation Genomics, University of Ulm, Ulm, Germany; Group Morcegos de Galicia, Drosera Society, Pdo. Magdalena, As Pontes, Spain 
8  Institute for Pharmacology and Toxicology, University of Bonn, Bonn, Germany 
Pages
1-11
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-33487-8
ProQuest document ID
2118359402
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.