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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.

Authors :
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
Drexler, Jan Felix
Müller, Marcel Alexander
Drosten, Christian
Source :
Scientific Reports; 10/11/2018, Vol. 8 Issue 1, p1-1, 1p
Publication Year :
2018

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20452322
Volume :
8
Issue :
1
Database :
Complementary Index
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
132323489
Full Text :
https://doi.org/10.1038/s41598-018-33487-8