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

Muth, Doreen; Corman, Victor Max; Roth, Hanna; Binger, Tabea; Dijkman, Ronald; Gottula, Lina Theresa; Gloza-Rausch, Florian; Balboni, Andrea; Battilani, Mara; Rihtarič, Danijela; Toplak, Ivan; Ameneiros, Ramón Seage; Pfeifer, Alexander; Thiel, Volker Earl; Drexler, Jan Felix; Müller, Marcel Alexander; Drosten, Christian (2018). Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission. Scientific Reports, 8(1), p. 15177. Nature Publishing Group 10.1038/s41598-018-33487-8

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction

UniBE Contributor:

Dijkman, Ronald and Thiel, Volker Earl

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

21 May 2019 15:42

Last Modified:

23 Oct 2019 05:35

Publisher DOI:

10.1038/s41598-018-33487-8

PubMed ID:

30310104

BORIS DOI:

10.7892/boris.127520

URI:

https://boris.unibe.ch/id/eprint/127520

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