Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice
Identifieur interne : 003000 ( Main/Exploration ); précédent : 002F99; suivant : 003001Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice
Auteurs : Michelle M. Becker ; Rachel L. Graham ; Eric F. Donaldson ; Barry Rockx ; Amy C. Sims [États-Unis] ; Timothy Sheahan ; Raymond J. Pickles ; Davide Corti [Suisse] ; Robert E. Johnston [États-Unis] ; Ralph S. Baric [États-Unis] ; Mark R. Denison [États-Unis]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2008.
Descripteurs français
- KwdFr :
- Animaux, Cellules Vero, Cellules cultivées, Chiroptera (virologie), Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Humains, Muqueuse respiratoire (virologie), Protéines de l'enveloppe virale (génétique), Protéines recombinantes (génétique), Recombinaison génétique, Réplication virale, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (virologie), Séquence d'acides aminés, Virus du SRAS (génétique), Virus du SRAS (isolement et purification), Virus du SRAS (physiologie), Zoonoses (transmission), Zoonoses (virologie).
- MESH :
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Protéines recombinantes, Virus du SRAS.
- isolement et purification : Virus du SRAS.
- physiologie : Virus du SRAS.
- virologie : Chiroptera, Muqueuse respiratoire, Syndrome respiratoire aigu sévère, Zoonoses.
- transmission : Animaux, Cellules Vero, Cellules cultivées, Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus, Humains, Recombinaison génétique, Réplication virale, Souris, Souris de lignée BALB C, Séquence d'acides aminés, Zoonoses.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Cells, Cultured, Chiroptera (virology), Chlorocebus aethiops, Female, Humans, Membrane Glycoproteins (genetics), Mice, Mice, Inbred BALB C, Molecular Sequence Data, Recombinant Proteins (genetics), Recombination, Genetic, Respiratory Mucosa (virology), SARS Virus (genetics), SARS Virus (isolation & purification), SARS Virus (physiology), Severe Acute Respiratory Syndrome (virology), Spike Glycoprotein, Coronavirus, Vero Cells, Viral Envelope Proteins (genetics), Virus Replication, Zoonoses (transmission), Zoonoses (virology).
- MESH :
- chemical , genetics : Membrane Glycoproteins, Recombinant Proteins, Viral Envelope Proteins.
- genetics : SARS Virus.
- isolation & purification : SARS Virus.
- physiology : SARS Virus.
- transmission : Zoonoses.
- virology : Chiroptera, Respiratory Mucosa, Severe Acute Respiratory Syndrome, Zoonoses.
- Amino Acid Sequence, Animals, Cells, Cultured, Chlorocebus aethiops, Female, Humans, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Recombination, Genetic, Spike Glycoprotein, Coronavirus, Vero Cells, Virus Replication.
Abstract
Defining prospective pathways by which zoonoses evolve and emerge as human pathogens is critical for anticipating and controlling both natural and deliberate pandemics. However, predicting tenable pathways of animal-to-human movement has been hindered by challenges in identifying reservoir species, cultivating zoonotic organisms in culture, and isolating full-length genomes for cloning and genetic studies. The ability to design and recover pathogens reconstituted from synthesized cDNAs has the potential to overcome these obstacles by allowing studies of replication and pathogenesis without identification of reservoir species or cultivation of primary isolates. Here, we report the design, synthesis, and recovery of the largest synthetic replicating life form, a 29.7-kb bat severe acute respiratory syndrome (SARS)-like coronavirus (Bat-SCoV), a likely progenitor to the SARS-CoV epidemic. To test a possible route of emergence from the noncultivable Bat-SCoV to human SARS-CoV, we designed a consensus Bat-SCoV genome and replaced the Bat-SCoV Spike receptor-binding domain (RBD) with the SARS-CoV RBD (Bat-SRBD). Bat-SRBD was infectious in cell culture and in mice and was efficiently neutralized by antibodies specific for both bat and human CoV Spike proteins. Rational design, synthesis, and recovery of hypothetical recombinant viruses can be used to investigate mechanisms of transspecies movement of zoonoses and has great potential to aid in rapid public health responses to known or predicted emerging microbial threats.
Url:
DOI: 10.1073/pnas.0808116105
PubMed: 19036930
PubMed Central: 2588415
Affiliations:
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Le document en format XML
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<term>Animals</term>
<term>Cells, Cultured</term>
<term>Chiroptera (virology)</term>
<term>Chlorocebus aethiops</term>
<term>Female</term>
<term>Humans</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Sequence Data</term>
<term>Recombinant Proteins (genetics)</term>
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<term>SARS Virus (genetics)</term>
<term>SARS Virus (isolation & purification)</term>
<term>SARS Virus (physiology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Spike Glycoprotein, Coronavirus</term>
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<term>Viral Envelope Proteins (genetics)</term>
<term>Virus Replication</term>
<term>Zoonoses (transmission)</term>
<term>Zoonoses (virology)</term>
</keywords>
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<term>Femelle</term>
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<term>Muqueuse respiratoire (virologie)</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
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<term>Réplication virale</term>
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<term>Chlorocebus aethiops</term>
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<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Molecular Sequence Data</term>
<term>Recombination, Genetic</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Vero Cells</term>
<term>Virus Replication</term>
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<term>Recombinaison génétique</term>
<term>Réplication virale</term>
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<front><div type="abstract" xml:lang="en"><p>Defining prospective pathways by which zoonoses evolve and emerge as human pathogens is critical for anticipating and controlling both natural and deliberate pandemics. However, predicting tenable pathways of animal-to-human movement has been hindered by challenges in identifying reservoir species, cultivating zoonotic organisms in culture, and isolating full-length genomes for cloning and genetic studies. The ability to design and recover pathogens reconstituted from synthesized cDNAs has the potential to overcome these obstacles by allowing studies of replication and pathogenesis without identification of reservoir species or cultivation of primary isolates. Here, we report the design, synthesis, and recovery of the largest synthetic replicating life form, a 29.7-kb bat severe acute respiratory syndrome (SARS)-like coronavirus (Bat-SCoV), a likely progenitor to the SARS-CoV epidemic. To test a possible route of emergence from the noncultivable Bat-SCoV to human SARS-CoV, we designed a consensus Bat-SCoV genome and replaced the Bat-SCoV Spike receptor-binding domain (RBD) with the SARS-CoV RBD (Bat-SRBD). Bat-SRBD was infectious in cell culture and in mice and was efficiently neutralized by antibodies specific for both bat and human CoV Spike proteins. Rational design, synthesis, and recovery of hypothetical recombinant viruses can be used to investigate mechanisms of transspecies movement of zoonoses and has great potential to aid in rapid public health responses to known or predicted emerging microbial threats.</p>
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<name sortKey="Johnston, Robert E" sort="Johnston, Robert E" uniqKey="Johnston R" first="Robert E." last="Johnston">Robert E. Johnston</name>
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<country name="Suisse"><noRegion><name sortKey="Corti, Davide" sort="Corti, Davide" uniqKey="Corti D" first="Davide" last="Corti">Davide Corti</name>
</noRegion>
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</affiliations>
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