Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice▿
Identifieur interne : 003698 ( Main/Merge ); précédent : 003697; suivant : 003699Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice▿
Auteurs : Barry Rockx ; Timothy Sheahan ; Eric Donaldson ; Jack Harkema ; Amy Sims ; Mark Heise ; Raymond Pickles ; Mark Cameron ; David Kelvin ; Ralph BaricSource :
- Journal of Virology [ 0022-538X ] ; 2007.
Descripteurs français
- KwdFr :
- Amorces ADN, Animaux, Cellules Vero, Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (génétique), Mutation, Phylogénie, Poumon (anatomopathologie), Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (génétique), Réplication virale (génétique), Similitude de séquences d'acides aminés, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (anatomopathologie), Séquence d'acides aminés, Séquence nucléotidique, Virus du SRAS (), Virus du SRAS (isolement et purification), Virus du SRAS (pathogénicité), Zoonoses.
- MESH :
- anatomopathologie : Poumon, Syndrome respiratoire aigu sévère.
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Réplication virale.
- isolement et purification : Virus du SRAS.
- pathogénicité : Virus du SRAS.
- Amorces ADN, Animaux, Cellules Vero, Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Mutation, Phylogénie, Protéines de l'enveloppe virale, Similitude de séquences d'acides aminés, Souris, Souris de lignée BALB C, Séquence d'acides aminés, Séquence nucléotidique, Virus du SRAS, Zoonoses.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Base Sequence, Chlorocebus aethiops, DNA Primers, Female, Lung (pathology), Membrane Glycoproteins (chemistry), Membrane Glycoproteins (genetics), Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Phylogeny, SARS Virus (chemistry), SARS Virus (isolation & purification), SARS Virus (pathogenicity), Sequence Homology, Amino Acid, Severe Acute Respiratory Syndrome (pathology), Spike Glycoprotein, Coronavirus, Vero Cells, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (genetics), Virus Replication (genetics), Zoonoses.
- MESH :
- chemical , chemistry : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical : DNA Primers, Spike Glycoprotein, Coronavirus.
- chemistry : SARS Virus.
- genetics : Virus Replication.
- isolation & purification : SARS Virus.
- pathogenicity : SARS Virus.
- pathology : Lung, Severe Acute Respiratory Syndrome.
- Amino Acid Sequence, Animals, Base Sequence, Chlorocebus aethiops, Female, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Phylogeny, Sequence Homology, Amino Acid, Vero Cells, Zoonoses.
Abstract
The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly.
Url:
DOI: 10.1128/JVI.00505-07
PubMed: 17507479
PubMed Central: 1933338
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PMC:1933338Le document en format XML
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xml:lang="en" level="a" type="main">Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice<xref ref-type="fn" rid="fn1">▿</xref> </title><author><name sortKey="Rockx, Barry" sort="Rockx, Barry" uniqKey="Rockx B" first="Barry" last="Rockx">Barry Rockx</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Sheahan, Timothy" sort="Sheahan, Timothy" uniqKey="Sheahan T" first="Timothy" last="Sheahan">Timothy Sheahan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Donaldson, Eric" sort="Donaldson, Eric" uniqKey="Donaldson E" first="Eric" last="Donaldson">Eric Donaldson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Harkema, Jack" sort="Harkema, Jack" uniqKey="Harkema J" first="Jack" last="Harkema">Jack Harkema</name><affiliation><nlm:aff 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C</term><term>Molecular Sequence Data</term><term>Mutation</term><term>Phylogeny</term><term>SARS Virus (chemistry)</term><term>SARS Virus (isolation & purification)</term><term>SARS Virus (pathogenicity)</term><term>Sequence Homology, Amino Acid</term><term>Severe Acute Respiratory Syndrome (pathology)</term><term>Spike Glycoprotein, Coronavirus</term><term>Vero Cells</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (genetics)</term><term>Virus Replication (genetics)</term><term>Zoonoses</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amorces ADN</term><term>Animaux</term><term>Cellules Vero</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (génétique)</term><term>Mutation</term><term>Phylogénie</term><term>Poumon (anatomopathologie)</term><term>Protéines de l'enveloppe virale 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qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Réplication virale</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Base Sequence</term><term>Chlorocebus aethiops</term><term>Female</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Molecular Sequence Data</term><term>Mutation</term><term>Phylogeny</term><term>Sequence Homology, Amino Acid</term><term>Vero Cells</term><term>Zoonoses</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Amorces ADN</term><term>Animaux</term><term>Cellules Vero</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Mutation</term><term>Phylogénie</term><term>Protéines de l'enveloppe virale</term><term>Similitude de séquences d'acides aminés</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Séquence d'acides aminés</term><term>Séquence nucléotidique</term><term>Virus du SRAS</term><term>Zoonoses</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle- and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly.</p></div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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