A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties
Identifieur interne : 001408 ( Main/Exploration ); précédent : 001407; suivant : 001409A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties
Auteurs : Jean Kaoru Millet [États-Unis] ; Monty E. Goldstein [États-Unis] ; Rachael N. Labitt [États-Unis] ; Hung-Lun Hsu [États-Unis] ; Susan Daniel [États-Unis] ; Gary R. Whittaker [États-Unis]Source :
- Emerging Microbes & Infections [ 2222-1751 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Chameaux (virologie), Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Furine (métabolisme), Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (métabolisme), Humains, Isoleucine (génétique), Lignée cellulaire, Protéolyse, Pénétration virale, Substitution d'acide aminé, Sérine (génétique).
- MESH :
- génétique : Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Isoleucine, Sérine.
- isolement et purification : Coronavirus du syndrome respiratoire du Moyen-Orient.
- métabolisme : Furine, Glycoprotéine de spicule des coronavirus.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Chameaux.
- Animaux, Humains, Lignée cellulaire, Protéolyse, Pénétration virale, Substitution d'acide aminé.
English descriptors
- KwdEn :
- Amino Acid Substitution, Animals, Camelus (virology), Cell Line, Furin (metabolism), Humans, Isoleucine (genetics), Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (isolation & purification), Middle East Respiratory Syndrome Coronavirus (physiology), Proteolysis, Serine (genetics), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (metabolism), Virus Internalization.
- MESH :
- chemical , genetics : Isoleucine, Serine, Spike Glycoprotein, Coronavirus.
- chemical , metabolism : Furin, Spike Glycoprotein, Coronavirus.
- genetics : Middle East Respiratory Syndrome Coronavirus.
- isolation & purification : Middle East Respiratory Syndrome Coronavirus.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- virology : Camelus.
- Amino Acid Substitution, Animals, Cell Line, Humans, Proteolysis, Virus Internalization.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution.
Url:
DOI: 10.1038/emi.2016.125
PubMed: 27999426
PubMed Central: 5180369
Affiliations:
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Whittaker</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University</institution>, Ithaca, NY 14853,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Emerging Microbes & Infections</title><idno type="eISSN">2222-1751</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Substitution</term><term>Animals</term><term>Camelus (virology)</term><term>Cell Line</term><term>Furin (metabolism)</term><term>Humans</term><term>Isoleucine (genetics)</term><term>Middle East Respiratory Syndrome Coronavirus (genetics)</term><term>Middle East Respiratory Syndrome Coronavirus (isolation & purification)</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Proteolysis</term><term>Serine (genetics)</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (metabolism)</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Chameaux (virologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term><term>Furine (métabolisme)</term><term>Glycoprotéine de spicule des coronavirus (génétique)</term><term>Glycoprotéine de spicule des coronavirus (métabolisme)</term><term>Humains</term><term>Isoleucine (génétique)</term><term>Lignée cellulaire</term><term>Protéolyse</term><term>Pénétration virale</term><term>Substitution d'acide aminé</term><term>Sérine (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Isoleucine</term><term>Serine</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Furin</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Glycoprotéine de spicule des coronavirus</term><term>Isoleucine</term><term>Sérine</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Furine</term><term>Glycoprotéine de spicule des coronavirus</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Chameaux</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Camelus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Substitution</term><term>Animals</term><term>Cell Line</term><term>Humans</term><term>Proteolysis</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Lignée cellulaire</term><term>Protéolyse</term><term>Pénétration virale</term><term>Substitution d'acide aminé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Millet, Jean Kaoru" sort="Millet, Jean Kaoru" uniqKey="Millet J" first="Jean Kaoru" last="Millet">Jean Kaoru Millet</name></noRegion><name sortKey="Daniel, Susan" sort="Daniel, Susan" uniqKey="Daniel S" first="Susan" last="Daniel">Susan Daniel</name><name sortKey="Goldstein, Monty E" sort="Goldstein, Monty E" uniqKey="Goldstein M" first="Monty E" last="Goldstein">Monty E. Goldstein</name><name sortKey="Goldstein, Monty E" sort="Goldstein, Monty E" uniqKey="Goldstein M" first="Monty E" last="Goldstein">Monty E. Goldstein</name><name sortKey="Hsu, Hung Lun" sort="Hsu, Hung Lun" uniqKey="Hsu H" first="Hung-Lun" last="Hsu">Hung-Lun Hsu</name><name sortKey="Hsu, Hung Lun" sort="Hsu, Hung Lun" uniqKey="Hsu H" first="Hung-Lun" last="Hsu">Hung-Lun Hsu</name><name sortKey="Labitt, Rachael N" sort="Labitt, Rachael N" uniqKey="Labitt R" first="Rachael N" last="Labitt">Rachael N. Labitt</name><name sortKey="Labitt, Rachael N" sort="Labitt, Rachael N" uniqKey="Labitt R" first="Rachael N" last="Labitt">Rachael N. Labitt</name><name sortKey="Whittaker, Gary R" sort="Whittaker, Gary R" uniqKey="Whittaker G" first="Gary R" last="Whittaker">Gary R. Whittaker</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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