Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism.
Identifieur interne : 001055 ( Main/Exploration ); précédent : 001054; suivant : 001056Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism.
Auteurs : Jung-Eun Park [États-Unis] ; Kun Li [États-Unis] ; Arlene Barlan [États-Unis] ; Anthony R. Fehr [États-Unis] ; Stanley Perlman [États-Unis] ; Paul B. Mccray [États-Unis] ; Tom Gallagher [États-Unis]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2016.
Descripteurs français
- KwdFr :
- Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Glycoprotéine de spicule des coronavirus (génétique), Humains, Infections à coronavirus (génétique), Infections à coronavirus (virologie), Mutation, Poumon (anatomopathologie), Poumon (virologie), Protéolyse, Pénétration virale, Régulation de l'expression des gènes viraux, Tropisme viral (génétique), Virion (croissance et développement), Virion (génétique).
- MESH :
- anatomopathologie : Poumon.
- croissance et développement : Virion.
- génétique : Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Infections à coronavirus, Tropisme viral, Virion.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections à coronavirus, Poumon.
- Humains, Mutation, Protéolyse, Pénétration virale, Régulation de l'expression des gènes viraux.
English descriptors
- KwdEn :
- Coronavirus Infections (genetics), Coronavirus Infections (virology), Gene Expression Regulation, Viral, Humans, Lung (pathology), Lung (virology), Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Mutation, Proteolysis, Spike Glycoprotein, Coronavirus (genetics), Viral Tropism (genetics), Virion (genetics), Virion (growth & development), Virus Internalization.
- MESH :
- chemical , genetics : Spike Glycoprotein, Coronavirus.
- genetics : Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus, Viral Tropism, Virion.
- growth & development : Virion.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- pathology : Lung.
- virology : Coronavirus Infections, Lung.
- Gene Expression Regulation, Viral, Humans, Mutation, Proteolysis, Virus Internalization.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans from zoonotic sources and causes severe pulmonary disease. Virions require spike (S) glycoproteins for binding to cell receptors and for catalyzing virus-cell membrane fusion. Fusion occurs only after S proteins are cleaved sequentially, first during their secretion through the exocytic organelles of virus-producing cells, and second after virus binding to target-cell receptors. To more precisely determine how sequential proteolysis contributes to CoV infection, we introduced S mutations obstructing the first cleavages. These mutations severely compromised MERS-CoV infection into human lung-derived cells, but had little effect on infection into several other cell types. These cell type-specific requirements for proteolysis correlated with S conformations during cell entry. Without the first cleavages, S proteins resisted cell receptor-induced conformational changes, which restricted the second, fusion-activating cleavages. Consistent with these findings, precleaved MERS viruses used receptor-proximal, cell-surface proteases to effect the second fusion-activating cleavages during cell entry, whereas the more rigid uncleaved MERS viruses trafficked past these cell-surface proteases and into endosomes. Uncleaved viruses were less infectious to human airway epithelial and Calu3 cell cultures because they lacked sufficient endosomal fusion-activating proteases. Thus, by sensitizing viruses to receptor-induced conformational changes, the first S cleavages expand virus tropism to cell types that are relevant to lung infection, and therefore may be significant determinants of MERS-CoV virulence.
DOI: 10.1073/pnas.1608147113
PubMed: 27791014
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000F20
- to stream PubMed, to step Curation: 000F20
- to stream PubMed, to step Checkpoint: 000F34
- to stream Ncbi, to step Merge: 001822
- to stream Ncbi, to step Curation: 001822
- to stream Ncbi, to step Checkpoint: 001822
- to stream Main, to step Merge: 001059
- to stream Main, to step Curation: 001055
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism.</title><author><name sortKey="Park, Jung Eun" sort="Park, Jung Eun" uniqKey="Park J" first="Jung-Eun" last="Park">Jung-Eun Park</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, Loyola University Chicago, Maywood</wicri:cityArea></affiliation></author><author><name sortKey="Li, Kun" sort="Li, Kun" uniqKey="Li K" first="Kun" last="Li">Kun Li</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, University of Iowa, Iowa City, IA 52242.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pediatrics, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Barlan, Arlene" sort="Barlan, Arlene" uniqKey="Barlan A" first="Arlene" last="Barlan">Arlene Barlan</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, Loyola University Chicago, Maywood</wicri:cityArea></affiliation></author><author><name sortKey="Fehr, Anthony R" sort="Fehr, Anthony R" uniqKey="Fehr A" first="Anthony R" last="Fehr">Anthony R. Fehr</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, University of Iowa, Iowa City, IA 52242.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Microbiology, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, University of Iowa, Iowa City, IA 52242; Department of Microbiology, University of Iowa, Iowa City, IA 52242.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pediatrics, University of Iowa, Iowa City, IA 52242; Department of Microbiology, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B" last="Mccray">Paul B. Mccray</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, University of Iowa, Iowa City, IA 52242; Department of Microbiology, University of Iowa, Iowa City, IA 52242.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pediatrics, University of Iowa, Iowa City, IA 52242; Department of Microbiology, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Gallagher, Tom" sort="Gallagher, Tom" uniqKey="Gallagher T" first="Tom" last="Gallagher">Tom Gallagher</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153; tgallag@luc.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Loyola University Chicago, Maywood</wicri:regionArea><wicri:noRegion>Maywood</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27791014</idno><idno type="pmid">27791014</idno><idno type="doi">10.1073/pnas.1608147113</idno><idno type="wicri:Area/PubMed/Corpus">000F20</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000F20</idno><idno type="wicri:Area/PubMed/Curation">000F20</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000F20</idno><idno type="wicri:Area/PubMed/Checkpoint">000F34</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000F34</idno><idno type="wicri:Area/Ncbi/Merge">001822</idno><idno type="wicri:Area/Ncbi/Curation">001822</idno><idno type="wicri:Area/Ncbi/Checkpoint">001822</idno><idno type="wicri:Area/Main/Merge">001059</idno><idno type="wicri:Area/Main/Curation">001055</idno><idno type="wicri:Area/Main/Exploration">001055</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism.</title><author><name sortKey="Park, Jung Eun" sort="Park, Jung Eun" uniqKey="Park J" first="Jung-Eun" last="Park">Jung-Eun Park</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, Loyola University Chicago, Maywood</wicri:cityArea></affiliation></author><author><name sortKey="Li, Kun" sort="Li, Kun" uniqKey="Li K" first="Kun" last="Li">Kun Li</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, University of Iowa, Iowa City, IA 52242.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pediatrics, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Barlan, Arlene" sort="Barlan, Arlene" uniqKey="Barlan A" first="Arlene" last="Barlan">Arlene Barlan</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Microbiology and Immunology, Loyola University Chicago, Maywood</wicri:cityArea></affiliation></author><author><name sortKey="Fehr, Anthony R" sort="Fehr, Anthony R" uniqKey="Fehr A" first="Anthony R" last="Fehr">Anthony R. Fehr</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, University of Iowa, Iowa City, IA 52242.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Microbiology, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, University of Iowa, Iowa City, IA 52242; Department of Microbiology, University of Iowa, Iowa City, IA 52242.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pediatrics, University of Iowa, Iowa City, IA 52242; Department of Microbiology, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B" last="Mccray">Paul B. Mccray</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, University of Iowa, Iowa City, IA 52242; Department of Microbiology, University of Iowa, Iowa City, IA 52242.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Iowa</region></placeName><wicri:cityArea>Department of Pediatrics, University of Iowa, Iowa City, IA 52242; Department of Microbiology, University of Iowa, Iowa City</wicri:cityArea></affiliation></author><author><name sortKey="Gallagher, Tom" sort="Gallagher, Tom" uniqKey="Gallagher T" first="Tom" last="Gallagher">Tom Gallagher</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153; tgallag@luc.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Loyola University Chicago, Maywood</wicri:regionArea><wicri:noRegion>Maywood</wicri:noRegion></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus Infections (genetics)</term><term>Coronavirus Infections (virology)</term><term>Gene Expression Regulation, Viral</term><term>Humans</term><term>Lung (pathology)</term><term>Lung (virology)</term><term>Middle East Respiratory Syndrome Coronavirus (genetics)</term><term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term><term>Mutation</term><term>Proteolysis</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Viral Tropism (genetics)</term><term>Virion (genetics)</term><term>Virion (growth & development)</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term><term>Glycoprotéine de spicule des coronavirus (génétique)</term><term>Humains</term><term>Infections à coronavirus (génétique)</term><term>Infections à coronavirus (virologie)</term><term>Mutation</term><term>Poumon (anatomopathologie)</term><term>Poumon (virologie)</term><term>Protéolyse</term><term>Pénétration virale</term><term>Régulation de l'expression des gènes viraux</term><term>Tropisme viral (génétique)</term><term>Virion (croissance et développement)</term><term>Virion (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Virion</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus Infections</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>Viral Tropism</term><term>Virion</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Virion</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>Infections à coronavirus</term><term>Tropisme viral</term><term>Virion</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Gene Expression Regulation, Viral</term><term>Humans</term><term>Mutation</term><term>Proteolysis</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Mutation</term><term>Protéolyse</term><term>Pénétration virale</term><term>Régulation de l'expression des gènes viraux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans from zoonotic sources and causes severe pulmonary disease. Virions require spike (S) glycoproteins for binding to cell receptors and for catalyzing virus-cell membrane fusion. Fusion occurs only after S proteins are cleaved sequentially, first during their secretion through the exocytic organelles of virus-producing cells, and second after virus binding to target-cell receptors. To more precisely determine how sequential proteolysis contributes to CoV infection, we introduced S mutations obstructing the first cleavages. These mutations severely compromised MERS-CoV infection into human lung-derived cells, but had little effect on infection into several other cell types. These cell type-specific requirements for proteolysis correlated with S conformations during cell entry. Without the first cleavages, S proteins resisted cell receptor-induced conformational changes, which restricted the second, fusion-activating cleavages. Consistent with these findings, precleaved MERS viruses used receptor-proximal, cell-surface proteases to effect the second fusion-activating cleavages during cell entry, whereas the more rigid uncleaved MERS viruses trafficked past these cell-surface proteases and into endosomes. Uncleaved viruses were less infectious to human airway epithelial and Calu3 cell cultures because they lacked sufficient endosomal fusion-activating proteases. Thus, by sensitizing viruses to receptor-induced conformational changes, the first S cleavages expand virus tropism to cell types that are relevant to lung infection, and therefore may be significant determinants of MERS-CoV virulence.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li><li>Iowa</li></region></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Park, Jung Eun" sort="Park, Jung Eun" uniqKey="Park J" first="Jung-Eun" last="Park">Jung-Eun Park</name></region><name sortKey="Barlan, Arlene" sort="Barlan, Arlene" uniqKey="Barlan A" first="Arlene" last="Barlan">Arlene Barlan</name><name sortKey="Fehr, Anthony R" sort="Fehr, Anthony R" uniqKey="Fehr A" first="Anthony R" last="Fehr">Anthony R. Fehr</name><name sortKey="Gallagher, Tom" sort="Gallagher, Tom" uniqKey="Gallagher T" first="Tom" last="Gallagher">Tom Gallagher</name><name sortKey="Li, Kun" sort="Li, Kun" uniqKey="Li K" first="Kun" last="Li">Kun Li</name><name sortKey="Mccray, Paul B" sort="Mccray, Paul B" uniqKey="Mccray P" first="Paul B" last="Mccray">Paul B. Mccray</name><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001055 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001055 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:27791014
|texte= Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:27791014" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |