Identification of a new region of SARS-CoV S protein critical for viral entry.
Identifieur interne : 002B01 ( Main/Exploration ); précédent : 002B00; suivant : 002B02Identification of a new region of SARS-CoV S protein critical for viral entry.
Auteurs : Ying Guo [États-Unis] ; Jennifer Tisoncik ; Susanna Mcreynolds ; Michael Farzan ; Bellur S. Prabhakar ; Thomas Gallagher ; Lijun Rong ; Michael CaffreySource :
- Journal of molecular biology [ 1089-8638 ] ; 2009.
Descripteurs français
- KwdFr :
- Antiviraux (pharmacologie), Concentration inhibitrice 50, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (métabolisme), Humains, Interactions hôte-pathogène (), Lignée cellulaire, Mutagenèse dirigée, Peptides (pharmacologie), Peptidyl-Dipeptidase A (métabolisme), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (métabolisme), Pénétration virale, Récepteurs viraux (métabolisme), Substitution d'acide aminé (génétique), VIH (Virus de l'Immunodéficience Humaine) (génétique), Virus du SRAS (physiologie).
- MESH :
- génétique : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Substitution d'acide aminé, VIH (Virus de l'Immunodéficience Humaine).
- métabolisme : Glycoprotéines membranaires, Peptidyl-Dipeptidase A, Protéines de l'enveloppe virale, Récepteurs viraux.
- pharmacologie : Antiviraux, Peptides.
- physiologie : Virus du SRAS.
- Concentration inhibitrice 50, Glycoprotéine de spicule des coronavirus, Humains, Interactions hôte-pathogène, Lignée cellulaire, Mutagenèse dirigée, Pénétration virale.
English descriptors
- KwdEn :
- Amino Acid Substitution (genetics), Antiviral Agents (pharmacology), Cell Line, HIV (genetics), Host-Pathogen Interactions (drug effects), Humans, Inhibitory Concentration 50, Membrane Glycoproteins (genetics), Membrane Glycoproteins (metabolism), Mutagenesis, Site-Directed, Peptides (pharmacology), Peptidyl-Dipeptidase A (metabolism), Receptors, Virus (metabolism), SARS Virus (physiology), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism), Virus Internalization.
- MESH :
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Membrane Glycoproteins, Peptidyl-Dipeptidase A, Receptors, Virus, Viral Envelope Proteins.
- chemical , pharmacology : Antiviral Agents, Peptides.
- drug effects : Host-Pathogen Interactions.
- genetics : Amino Acid Substitution, HIV.
- physiology : SARS Virus.
- Cell Line, Humans, Inhibitory Concentration 50, Mutagenesis, Site-Directed, Spike Glycoprotein, Coronavirus, Virus Internalization.
Abstract
Infection by severe acute respiratory syndrome coronavirus (SARS-CoV) is initiated by specific interactions between the SARS-CoV spike (S) protein and its receptor ACE2. In this report, we screened a peptide library representing the SARS-CoV S protein sequence using a human immunodeficiency virus-based pseudotyping system to identify specific regions that affect viral entry. One of the 169 peptides screened, peptide 9626 (S residues 217-234), inhibited SARS-CoV S-mediated entry of the pseudotyped virions in 293T cells expressing a functional SARS-CoV receptor (human angiotensin-converting enzyme 2) in a dose-dependent manner (IC(50) approximately 11 microM). Alanine scanning mutagenesis was performed to assess the roles of individual residues within this region of S, which was previously uncharacterized. The effects included significant reductions in expression (K223A), viral incorporation (L218A, I230A, and N232A), and reduced viral entry (L224A, L226A, I228A, T231A, and F233A). Taken together, these results reveal a new region of the S protein that is crucial for SARS-CoV entry.
DOI: 10.1016/j.jmb.2009.10.032
PubMed: 19853613
Affiliations:
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Le document en format XML
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Prabhakar</name></author><author><name sortKey="Gallagher, Thomas" sort="Gallagher, Thomas" uniqKey="Gallagher T" first="Thomas" last="Gallagher">Thomas Gallagher</name></author><author><name sortKey="Rong, Lijun" sort="Rong, Lijun" uniqKey="Rong L" first="Lijun" last="Rong">Lijun Rong</name></author><author><name sortKey="Caffrey, Michael" sort="Caffrey, Michael" uniqKey="Caffrey M" first="Michael" last="Caffrey">Michael Caffrey</name></author></analytic><series><title level="j">Journal of molecular biology</title><idno type="eISSN">1089-8638</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Substitution (genetics)</term><term>Antiviral Agents (pharmacology)</term><term>Cell Line</term><term>HIV (genetics)</term><term>Host-Pathogen Interactions (drug effects)</term><term>Humans</term><term>Inhibitory Concentration 50</term><term>Membrane Glycoproteins (genetics)</term><term>Membrane Glycoproteins (metabolism)</term><term>Mutagenesis, Site-Directed</term><term>Peptides (pharmacology)</term><term>Peptidyl-Dipeptidase A (metabolism)</term><term>Receptors, Virus (metabolism)</term><term>SARS Virus (physiology)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (metabolism)</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antiviraux (pharmacologie)</term><term>Concentration inhibitrice 50</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (génétique)</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Humains</term><term>Interactions hôte-pathogène ()</term><term>Lignée cellulaire</term><term>Mutagenèse dirigée</term><term>Peptides (pharmacologie)</term><term>Peptidyl-Dipeptidase A (métabolisme)</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Pénétration virale</term><term>Récepteurs viraux (métabolisme)</term><term>Substitution d'acide aminé (génétique)</term><term>VIH (Virus de l'Immunodéficience Humaine) (génétique)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Membrane Glycoproteins</term><term>Peptidyl-Dipeptidase A</term><term>Receptors, Virus</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Host-Pathogen Interactions</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Amino Acid Substitution</term><term>HIV</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Substitution d'acide aminé</term><term>VIH (Virus de l'Immunodéficience Humaine)</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de l'enveloppe virale</term><term>Récepteurs viraux</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Peptides</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" xml:lang="en"><term>Cell Line</term><term>Humans</term><term>Inhibitory Concentration 50</term><term>Mutagenesis, Site-Directed</term><term>Spike Glycoprotein, Coronavirus</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Concentration inhibitrice 50</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Lignée cellulaire</term><term>Mutagenèse dirigée</term><term>Pénétration virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Infection by severe acute respiratory syndrome coronavirus (SARS-CoV) is initiated by specific interactions between the SARS-CoV spike (S) protein and its receptor ACE2. In this report, we screened a peptide library representing the SARS-CoV S protein sequence using a human immunodeficiency virus-based pseudotyping system to identify specific regions that affect viral entry. One of the 169 peptides screened, peptide 9626 (S residues 217-234), inhibited SARS-CoV S-mediated entry of the pseudotyped virions in 293T cells expressing a functional SARS-CoV receptor (human angiotensin-converting enzyme 2) in a dose-dependent manner (IC(50) approximately 11 microM). Alanine scanning mutagenesis was performed to assess the roles of individual residues within this region of S, which was previously uncharacterized. The effects included significant reductions in expression (K223A), viral incorporation (L218A, I230A, and N232A), and reduced viral entry (L224A, L226A, I228A, T231A, and F233A). Taken together, these results reveal a new region of the S protein that is crucial for SARS-CoV entry.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li></region><settlement><li>Chicago</li></settlement><orgName><li>Université de l'Illinois à Chicago</li></orgName></list><tree><noCountry><name sortKey="Caffrey, Michael" sort="Caffrey, Michael" uniqKey="Caffrey M" first="Michael" last="Caffrey">Michael Caffrey</name><name sortKey="Farzan, Michael" sort="Farzan, Michael" uniqKey="Farzan M" first="Michael" last="Farzan">Michael Farzan</name><name sortKey="Gallagher, Thomas" sort="Gallagher, Thomas" uniqKey="Gallagher T" first="Thomas" last="Gallagher">Thomas Gallagher</name><name sortKey="Mcreynolds, Susanna" sort="Mcreynolds, Susanna" uniqKey="Mcreynolds S" first="Susanna" last="Mcreynolds">Susanna Mcreynolds</name><name sortKey="Prabhakar, Bellur S" sort="Prabhakar, Bellur S" uniqKey="Prabhakar B" first="Bellur S" last="Prabhakar">Bellur S. Prabhakar</name><name sortKey="Rong, Lijun" sort="Rong, Lijun" uniqKey="Rong L" first="Lijun" last="Rong">Lijun Rong</name><name sortKey="Tisoncik, Jennifer" sort="Tisoncik, Jennifer" uniqKey="Tisoncik J" first="Jennifer" last="Tisoncik">Jennifer Tisoncik</name></noCountry><country name="États-Unis"><region name="Illinois"><name sortKey="Guo, Ying" sort="Guo, Ying" uniqKey="Guo Y" first="Ying" last="Guo">Ying Guo</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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