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

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. H...

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Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2018
Materias:
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoVs)
Nt Deletion
Human Angiotensin-converting Enzyme
Full ORF8
Human Airway Epithelial Cultures (HAE)
Medicine
R
Science
Q
Acceso en línea:https://doaj.org/article/dc2eb990e1334c749f38f36a60836653
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Sumario: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.

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