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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2018
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oai:doaj.org-article:dc2eb990e1334c749f38f36a608366532021-12-02T15:07:47ZAttenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission10.1038/s41598-018-33487-82045-2322https://doaj.org/article/dc2eb990e1334c749f38f36a608366532018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33487-8https://doaj.org/toc/2045-2322Abstract 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.Doreen MuthVictor Max CormanHanna RothTabea BingerRonald DijkmanLina Theresa GottulaFlorian Gloza-RauschAndrea BalboniMara BattilaniDanijela RihtaričIvan ToplakRamón Seage AmeneirosAlexander PfeiferVolker ThielJan Felix DrexlerMarcel Alexander MüllerChristian DrostenNature PortfolioarticleSevere Acute Respiratory Syndrome Coronavirus (SARS-CoVs)Nt DeletionHuman Angiotensin-converting EnzymeFull ORF8Human Airway Epithelial Cultures (HAE)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) |
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Severe Acute Respiratory Syndrome Coronavirus (SARS-CoVs) Nt Deletion Human Angiotensin-converting Enzyme Full ORF8 Human Airway Epithelial Cultures (HAE) Medicine R Science Q |
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Severe Acute Respiratory Syndrome Coronavirus (SARS-CoVs) Nt Deletion Human Angiotensin-converting Enzyme Full ORF8 Human Airway Epithelial Cultures (HAE) Medicine R Science Q 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 Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Doreen Muth |
| title |
Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission |
| title_short |
Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission |
| title_full |
Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission |
| title_fullStr |
Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission |
| title_full_unstemmed |
Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission |
| title_sort |
attenuation of replication by a 29 nucleotide deletion in sars-coronavirus acquired during the early stages of human-to-human transmission |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/dc2eb990e1334c749f38f36a60836653 |
| work_keys_str_mv |
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1718388420199317504 |