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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

Identifieur interne : 000D17 ( Main/Exploration ); précédent : 000D16; suivant : 000D18

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

Auteurs : Doreen Muth [Allemagne] ; Victor Max Corman [Allemagne] ; Hanna Roth [Allemagne] ; Tabea Binger [Allemagne] ; Ronald Dijkman [Suisse] ; Lina Theresa Gottula [Allemagne] ; Florian Gloza-Rausch [Allemagne] ; Andrea Balboni ; Mara Battilani ; Danijela Rihtari [Slovénie] ; Ivan Toplak [Slovénie] ; Ram N Seage Ameneiros [Allemagne, Espagne] ; Alexander Pfeifer [Allemagne] ; Volker Thiel [Suisse] ; Jan Felix Drexler [Allemagne] ; Marcel Alexander Müller [Allemagne] ; Christian Drosten [Allemagne]

Source :

RBID : PMC:6181990

Descripteurs français

English descriptors

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.


Url:
DOI: 10.1038/s41598-018-33487-8
PubMed: 30310104
PubMed Central: 6181990


Affiliations:


Links toward previous steps (curation, corpus...)


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Berlin, Germany</nlm:aff>
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Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
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<title xml:lang="en" level="a" type="main">Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission</title>
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<name sortKey="Muth, Doreen" sort="Muth, Doreen" uniqKey="Muth D" first="Doreen" last="Muth">Doreen Muth</name>
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<country xml:lang="fr">Allemagne</country>
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Berlin, Germany</nlm:aff>
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Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
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<nlm:aff id="Aff1">Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff>
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Berlin, Germany</nlm:aff>
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Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
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<name sortKey="Roth, Hanna" sort="Roth, Hanna" uniqKey="Roth H" first="Hanna" last="Roth">Hanna Roth</name>
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Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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<settlement type="city">Bonn</settlement>
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<name sortKey="Binger, Tabea" sort="Binger, Tabea" uniqKey="Binger T" first="Tabea" last="Binger">Tabea Binger</name>
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<institution>University of Bonn Medical Centre,</institution>
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Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Sigmund-Freud-Str. 25, 53127 Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Dijkman, Ronald" sort="Dijkman, Ronald" uniqKey="Dijkman R" first="Ronald" last="Dijkman">Ronald Dijkman</name>
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<institution-wrap>
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<institution-id institution-id-type="ISNI">0000 0001 1250 5733</institution-id>
<institution>Federal Department of Home Affairs,</institution>
<institution>Institute of Virology and Immunology IVI, Bern and Mittelhäusern,</institution>
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Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Sensemattstrasse 293, 3147 Mittelhäusern</wicri:regionArea>
<wicri:noRegion>3147 Mittelhäusern</wicri:noRegion>
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<institution-id institution-id-type="GRID">grid.5734.5</institution-id>
<institution>Department of Infectious Diseases and Pathobiology,</institution>
<institution>Vetsuisse Faculty, University of Bern,</institution>
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Länggassstrasse 122, 3012 Bern, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Länggassstrasse 122, 3012 Bern</wicri:regionArea>
<placeName>
<settlement type="city">Berne</settlement>
<region type="région" nuts="3">Canton de Berne</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Gottula, Lina Theresa" sort="Gottula, Lina Theresa" uniqKey="Gottula L" first="Lina Theresa" last="Gottula">Lina Theresa Gottula</name>
<affiliation wicri:level="3">
<nlm:aff id="Aff1">Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117 Berlin</wicri:regionArea>
<placeName>
<region type="land" nuts="3">Berlin</region>
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Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Berlin</wicri:regionArea>
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Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
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</affiliation>
</author>
<author>
<name sortKey="Gloza Rausch, Florian" sort="Gloza Rausch, Florian" uniqKey="Gloza Rausch F" first="Florian" last="Gloza-Rausch">Florian Gloza-Rausch</name>
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<wicri:noRegion>23795 Bad Segeberg</wicri:noRegion>
<wicri:noRegion>23795 Bad Segeberg</wicri:noRegion>
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<nlm:aff id="Aff7">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0004 1757 1758</institution-id>
<institution-id institution-id-type="GRID">grid.6292.f</institution-id>
<institution>Dipartimento di Scienze Mediche Veterinarie,</institution>
<institution>Facoltà di Medicina Veterinaria, Alma Mater Studiorum-Università di Bologna,</institution>
</institution-wrap>
Via Tolara di Sopra 50, 40064 Ozzano Emilia, (BO) Italy</nlm:aff>
<wicri:noCountry code="subfield">(BO) Italy</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Battilani, Mara" sort="Battilani, Mara" uniqKey="Battilani M" first="Mara" last="Battilani">Mara Battilani</name>
<affiliation>
<nlm:aff id="Aff7">
<institution-wrap>
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<institution-id institution-id-type="GRID">grid.6292.f</institution-id>
<institution>Dipartimento di Scienze Mediche Veterinarie,</institution>
<institution>Facoltà di Medicina Veterinaria, Alma Mater Studiorum-Università di Bologna,</institution>
</institution-wrap>
Via Tolara di Sopra 50, 40064 Ozzano Emilia, (BO) Italy</nlm:aff>
<wicri:noCountry code="subfield">(BO) Italy</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Rihtari, Danijela" sort="Rihtari, Danijela" uniqKey="Rihtari D" first="Danijela" last="Rihtari">Danijela Rihtari</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff8">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 0721 6013</institution-id>
<institution-id institution-id-type="GRID">grid.8954.0</institution-id>
<institution>Virology Unit, Institute of Microbiology and Parasitology,</institution>
<institution>Veterinary Faculty, University of Ljubljana,</institution>
</institution-wrap>
Gerbičeva 60, 1000 Ljubljana, Slovenia</nlm:aff>
<country xml:lang="fr">Slovénie</country>
<wicri:regionArea>Gerbičeva 60, 1000 Ljubljana</wicri:regionArea>
<wicri:noRegion>1000 Ljubljana</wicri:noRegion>
</affiliation>
</author>
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<name sortKey="Toplak, Ivan" sort="Toplak, Ivan" uniqKey="Toplak I" first="Ivan" last="Toplak">Ivan Toplak</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff8">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 0721 6013</institution-id>
<institution-id institution-id-type="GRID">grid.8954.0</institution-id>
<institution>Virology Unit, Institute of Microbiology and Parasitology,</institution>
<institution>Veterinary Faculty, University of Ljubljana,</institution>
</institution-wrap>
Gerbičeva 60, 1000 Ljubljana, Slovenia</nlm:aff>
<country xml:lang="fr">Slovénie</country>
<wicri:regionArea>Gerbičeva 60, 1000 Ljubljana</wicri:regionArea>
<wicri:noRegion>1000 Ljubljana</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Ameneiros, Ram N Seage" sort="Ameneiros, Ram N Seage" uniqKey="Ameneiros R" first="Ram N Seage" last="Ameneiros">Ram N Seage Ameneiros</name>
<affiliation wicri:level="3">
<nlm:aff id="Aff9">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0004 1936 9748</institution-id>
<institution-id institution-id-type="GRID">grid.6582.9</institution-id>
<institution>Institute of Evolutionary Ecology and Conservation Genomics,</institution>
<institution>University of Ulm,</institution>
</institution-wrap>
Albert-Einstein Allee 11, 89069 Ulm, Germany</nlm:aff>
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<wicri:regionArea>Albert-Einstein Allee 11, 89069 Ulm</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
<settlement type="city">Ulm</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff10">Group Morcegos de Galicia, Drosera Society, Pdo. Magdalena, G-2, 2° esq, 15320 As Pontes, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Group Morcegos de Galicia, Drosera Society, Pdo. Magdalena, G-2, 2° esq, 15320 As Pontes</wicri:regionArea>
<placeName>
<region nuts="2" type="communauté">Galice</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Pfeifer, Alexander" sort="Pfeifer, Alexander" uniqKey="Pfeifer A" first="Alexander" last="Pfeifer">Alexander Pfeifer</name>
<affiliation wicri:level="3">
<nlm:aff id="Aff11">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2240 3300</institution-id>
<institution-id institution-id-type="GRID">grid.10388.32</institution-id>
<institution>Institute for Pharmacology and Toxicology,</institution>
<institution>University of Bonn,</institution>
</institution-wrap>
Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Sigmund-Freud-Str. 25, 53127 Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Thiel, Volker" sort="Thiel, Volker" uniqKey="Thiel V" first="Volker" last="Thiel">Volker Thiel</name>
<affiliation wicri:level="1">
<nlm:aff id="Aff4">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.424284.c</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 1250 5733</institution-id>
<institution>Federal Department of Home Affairs,</institution>
<institution>Institute of Virology and Immunology IVI, Bern and Mittelhäusern,</institution>
</institution-wrap>
Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Sensemattstrasse 293, 3147 Mittelhäusern</wicri:regionArea>
<wicri:noRegion>3147 Mittelhäusern</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff5">
<institution-wrap>
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<institution-id institution-id-type="GRID">grid.5734.5</institution-id>
<institution>Department of Infectious Diseases and Pathobiology,</institution>
<institution>Vetsuisse Faculty, University of Bern,</institution>
</institution-wrap>
Länggassstrasse 122, 3012 Bern, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Länggassstrasse 122, 3012 Bern</wicri:regionArea>
<placeName>
<settlement type="city">Berne</settlement>
<region type="région" nuts="3">Canton de Berne</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Drexler, Jan Felix" sort="Drexler, Jan Felix" uniqKey="Drexler J" first="Jan Felix" last="Drexler">Jan Felix Drexler</name>
<affiliation wicri:level="3">
<nlm:aff id="Aff1">Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117 Berlin</wicri:regionArea>
<placeName>
<region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.452463.2</institution-id>
<institution>German Center for Infection Research (DZIF),</institution>
</institution-wrap>
Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Berlin</wicri:regionArea>
</affiliation>
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<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0000 8786 803X</institution-id>
<institution-id institution-id-type="GRID">grid.15090.3d</institution-id>
<institution>Institute of Virology,</institution>
<institution>University of Bonn Medical Centre,</institution>
</institution-wrap>
Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Sigmund-Freud-Str. 25, 53127 Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Muller, Marcel Alexander" sort="Muller, Marcel Alexander" uniqKey="Muller M" first="Marcel Alexander" last="Müller">Marcel Alexander Müller</name>
<affiliation wicri:level="3">
<nlm:aff id="Aff1">Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117 Berlin</wicri:regionArea>
<placeName>
<region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.452463.2</institution-id>
<institution>German Center for Infection Research (DZIF),</institution>
</institution-wrap>
Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Berlin</wicri:regionArea>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0000 8786 803X</institution-id>
<institution-id institution-id-type="GRID">grid.15090.3d</institution-id>
<institution>Institute of Virology,</institution>
<institution>University of Bonn Medical Centre,</institution>
</institution-wrap>
Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Sigmund-Freud-Str. 25, 53127 Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
<affiliation wicri:level="3">
<nlm:aff id="Aff1">Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117 Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Charitéplatz 1, 10117 Berlin</wicri:regionArea>
<placeName>
<region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="GRID">grid.452463.2</institution-id>
<institution>German Center for Infection Research (DZIF),</institution>
</institution-wrap>
Berlin, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Berlin</wicri:regionArea>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0000 8786 803X</institution-id>
<institution-id institution-id-type="GRID">grid.15090.3d</institution-id>
<institution>Institute of Virology,</institution>
<institution>University of Bonn Medical Centre,</institution>
</institution-wrap>
Sigmund-Freud-Str. 25, 53127 Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Sigmund-Freud-Str. 25, 53127 Bonn</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Scientific Reports</title>
<idno type="eISSN">2045-2322</idno>
<imprint>
<date when="2018">2018</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Animals</term>
<term>Cell Line</term>
<term>Cells, Cultured</term>
<term>Chiroptera (virology)</term>
<term>Disease Reservoirs</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>RNA, Viral</term>
<term>Recombinant Proteins</term>
<term>SARS Virus (physiology)</term>
<term>Sequence Deletion</term>
<term>Severe Acute Respiratory Syndrome (transmission)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Viral Matrix Proteins (genetics)</term>
<term>Viral Matrix Proteins (metabolism)</term>
<term>Virus Replication (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>ARN viral</term>
<term>Animaux</term>
<term>Cellules cultivées</term>
<term>Chiroptera (virologie)</term>
<term>Délétion de séquence</term>
<term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Lignée cellulaire</term>
<term>Protéines de la matrice virale (génétique)</term>
<term>Protéines de la matrice virale (métabolisme)</term>
<term>Protéines recombinantes</term>
<term>Réplication virale (génétique)</term>
<term>Réservoirs d'agents pathogènes</term>
<term>Syndrome respiratoire aigu sévère (transmission)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virus du SRAS (physiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Viral Matrix Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Viral Matrix Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en">
<term>RNA, Viral</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Protéines de la matrice virale</term>
<term>Réplication virale</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Protéines de la matrice virale</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en">
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="transmission" xml:lang="en">
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Chiroptera</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Chiroptera</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Cell Line</term>
<term>Cells, Cultured</term>
<term>Disease Reservoirs</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Sequence Deletion</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>ARN viral</term>
<term>Animaux</term>
<term>Cellules cultivées</term>
<term>Délétion de séquence</term>
<term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Lignée cellulaire</term>
<term>Protéines recombinantes</term>
<term>Réservoirs d'agents pathogènes</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="Par1">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
<italic>Rhinolophus</italic>
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.</p>
</div>
</front>
<back>
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</author>
<author>
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<name sortKey="Matrosovich, T" uniqKey="Matrosovich T">T Matrosovich</name>
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<li>Allemagne</li>
<li>Espagne</li>
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<li>Suisse</li>
</country>
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<li>Bade-Wurtemberg</li>
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<li>District de Cologne</li>
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<name sortKey="Drexler, Jan Felix" sort="Drexler, Jan Felix" uniqKey="Drexler J" first="Jan Felix" last="Drexler">Jan Felix Drexler</name>
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<name sortKey="Gottula, Lina Theresa" sort="Gottula, Lina Theresa" uniqKey="Gottula L" first="Lina Theresa" last="Gottula">Lina Theresa Gottula</name>
<name sortKey="Muller, Marcel Alexander" sort="Muller, Marcel Alexander" uniqKey="Muller M" first="Marcel Alexander" last="Müller">Marcel Alexander Müller</name>
<name sortKey="Muller, Marcel Alexander" sort="Muller, Marcel Alexander" uniqKey="Muller M" first="Marcel Alexander" last="Müller">Marcel Alexander Müller</name>
<name sortKey="Muller, Marcel Alexander" sort="Muller, Marcel Alexander" uniqKey="Muller M" first="Marcel Alexander" last="Müller">Marcel Alexander Müller</name>
<name sortKey="Muth, Doreen" sort="Muth, Doreen" uniqKey="Muth D" first="Doreen" last="Muth">Doreen Muth</name>
<name sortKey="Muth, Doreen" sort="Muth, Doreen" uniqKey="Muth D" first="Doreen" last="Muth">Doreen Muth</name>
<name sortKey="Pfeifer, Alexander" sort="Pfeifer, Alexander" uniqKey="Pfeifer A" first="Alexander" last="Pfeifer">Alexander Pfeifer</name>
<name sortKey="Roth, Hanna" sort="Roth, Hanna" uniqKey="Roth H" first="Hanna" last="Roth">Hanna Roth</name>
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<name sortKey="Dijkman, Ronald" sort="Dijkman, Ronald" uniqKey="Dijkman R" first="Ronald" last="Dijkman">Ronald Dijkman</name>
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<name sortKey="Dijkman, Ronald" sort="Dijkman, Ronald" uniqKey="Dijkman R" first="Ronald" last="Dijkman">Ronald Dijkman</name>
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<country name="Espagne">
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<name sortKey="Ameneiros, Ram N Seage" sort="Ameneiros, Ram N Seage" uniqKey="Ameneiros R" first="Ram N Seage" last="Ameneiros">Ram N Seage Ameneiros</name>
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</record>

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