Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy.
Identifieur interne : 004803 ( Main/Exploration ); précédent : 004802; suivant : 004804Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy.
Auteurs : Xiu-Xia Qu [République populaire de Chine] ; Pei Hao ; Xi-Jun Song ; Si-Ming Jiang ; Yan-Xia Liu ; Pei-Gang Wang ; Xi Rao ; Huai-Dong Song ; Sheng-Yue Wang ; Yu Zuo ; Ai-Hua Zheng ; Min Luo ; Hua-Lin Wang ; Fei Deng ; Han-Zhong Wang ; Zhi-Hong Hu ; Ming-Xiao Ding ; Guo-Ping Zhao ; Hong-Kui DengSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2005.
Descripteurs français
- KwdFr :
- Carboxypeptidases (métabolisme), Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (physiologie), Humains, Peptidyl-Dipeptidase A, Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (physiologie), Relation structure-activité, Sites de fixation, Substitution d'acide aminé, Syndrome respiratoire aigu sévère (transmission), Séquence d'acides aminés, Tropisme, Virus du SRAS (), Virus du SRAS (pathogénicité), Zoonoses.
- MESH :
- métabolisme : Carboxypeptidases.
- pathogénicité : Virus du SRAS.
- physiologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Peptidyl-Dipeptidase A, Protéines de l'enveloppe virale, Relation structure-activité, Sites de fixation, Substitution d'acide aminé, Syndrome respiratoire aigu sévère, Séquence d'acides aminés, Tropisme, Virus du SRAS, Zoonoses.
English descriptors
- KwdEn :
- Amino Acid Sequence, Amino Acid Substitution, Binding Sites, Carboxypeptidases (metabolism), Humans, Membrane Glycoproteins (chemistry), Membrane Glycoproteins (physiology), Molecular Sequence Data, Peptidyl-Dipeptidase A, SARS Virus (chemistry), SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (transmission), Spike Glycoprotein, Coronavirus, Structure-Activity Relationship, Tropism, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (physiology), Zoonoses.
- MESH :
- chemical , chemistry : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Carboxypeptidases.
- chemical , physiology : Membrane Glycoproteins, Viral Envelope Proteins.
- chemistry : SARS Virus.
- pathogenicity : SARS Virus.
- transmission : Severe Acute Respiratory Syndrome.
- Amino Acid Sequence, Amino Acid Substitution, Binding Sites, Humans, Molecular Sequence Data, Peptidyl-Dipeptidase A, Spike Glycoprotein, Coronavirus, Structure-Activity Relationship, Tropism, Zoonoses.
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a recently identified human coronavirus. The extremely high homology of the viral genomic sequences between the viruses isolated from human (huSARS-CoV) and those of palm civet origin (pcSARS-CoV) suggested possible palm civet-to-human transmission. Genetic analysis revealed that the spike (S) protein of pcSARS-CoV and huSARS-CoV was subjected to the strongest positive selection pressure during transmission, and there were six amino acid residues within the receptor-binding domain of the S protein being potentially important for SARS progression and tropism. Using the single-round infection assay, we found that a two-amino acid substitution (N479K/T487S) of a huSARS-CoV for those of pcSARS-CoV almost abolished its infection of human cells expressing the SARS-CoV receptor ACE2 but no effect upon the infection of mouse ACE2 cells. Although single substitution of these two residues had no effects on the infectivity of huSARS-CoV, these recombinant S proteins bound to human ACE2 with different levels of reduced affinity, and the two-amino acid-substituted S protein showed extremely low affinity. On the contrary, substitution of these two amino acid residues of pcSARS-CoV for those of huSRAS-CoV made pcSARS-CoV capable of infecting human ACE2-expressing cells. These results suggest that amino acid residues at position 479 and 487 of the S protein are important determinants for SARS-CoV tropism and animal-to-human transmission.
DOI: 10.1074/jbc.M500662200
PubMed: 15980414
Affiliations:
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Le document en format XML
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University, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName><orgName type="university">Université de Pékin</orgName></affiliation></author><author><name sortKey="Hao, Pei" sort="Hao, Pei" uniqKey="Hao P" first="Pei" last="Hao">Pei Hao</name></author><author><name sortKey="Song, Xi Jun" sort="Song, Xi Jun" uniqKey="Song X" first="Xi-Jun" last="Song">Xi-Jun Song</name></author><author><name sortKey="Jiang, Si Ming" sort="Jiang, Si Ming" uniqKey="Jiang S" first="Si-Ming" last="Jiang">Si-Ming Jiang</name></author><author><name sortKey="Liu, Yan Xia" sort="Liu, Yan Xia" uniqKey="Liu Y" first="Yan-Xia" last="Liu">Yan-Xia Liu</name></author><author><name sortKey="Wang, Pei Gang" sort="Wang, Pei Gang" uniqKey="Wang P" first="Pei-Gang" last="Wang">Pei-Gang Wang</name></author><author><name sortKey="Rao, Xi" sort="Rao, Xi" uniqKey="Rao X" first="Xi" last="Rao">Xi Rao</name></author><author><name sortKey="Song, Huai Dong" sort="Song, Huai Dong" uniqKey="Song H" first="Huai-Dong" last="Song">Huai-Dong Song</name></author><author><name sortKey="Wang, Sheng Yue" sort="Wang, Sheng Yue" uniqKey="Wang S" first="Sheng-Yue" last="Wang">Sheng-Yue Wang</name></author><author><name sortKey="Zuo, Yu" sort="Zuo, Yu" uniqKey="Zuo Y" first="Yu" last="Zuo">Yu Zuo</name></author><author><name sortKey="Zheng, Ai Hua" sort="Zheng, Ai Hua" uniqKey="Zheng A" first="Ai-Hua" last="Zheng">Ai-Hua Zheng</name></author><author><name sortKey="Luo, Min" sort="Luo, Min" uniqKey="Luo M" first="Min" last="Luo">Min Luo</name></author><author><name sortKey="Wang, Hua Lin" sort="Wang, Hua Lin" uniqKey="Wang H" first="Hua-Lin" last="Wang">Hua-Lin Wang</name></author><author><name sortKey="Deng, Fei" sort="Deng, Fei" uniqKey="Deng F" first="Fei" last="Deng">Fei Deng</name></author><author><name sortKey="Wang, Han Zhong" sort="Wang, Han Zhong" uniqKey="Wang H" first="Han-Zhong" last="Wang">Han-Zhong Wang</name></author><author><name sortKey="Hu, Zhi Hong" sort="Hu, Zhi Hong" uniqKey="Hu Z" first="Zhi-Hong" last="Hu">Zhi-Hong Hu</name></author><author><name sortKey="Ding, Ming Xiao" sort="Ding, Ming Xiao" uniqKey="Ding M" first="Ming-Xiao" last="Ding">Ming-Xiao Ding</name></author><author><name sortKey="Zhao, Guo Ping" sort="Zhao, Guo Ping" uniqKey="Zhao G" first="Guo-Ping" last="Zhao">Guo-Ping Zhao</name></author><author><name sortKey="Deng, Hong Kui" sort="Deng, Hong Kui" uniqKey="Deng H" first="Hong-Kui" last="Deng">Hong-Kui Deng</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="ISSN">0021-9258</idno><imprint><date when="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Amino Acid Substitution</term><term>Binding Sites</term><term>Carboxypeptidases (metabolism)</term><term>Humans</term><term>Membrane Glycoproteins (chemistry)</term><term>Membrane Glycoproteins (physiology)</term><term>Molecular Sequence Data</term><term>Peptidyl-Dipeptidase A</term><term>SARS Virus (chemistry)</term><term>SARS Virus (pathogenicity)</term><term>Severe Acute Respiratory Syndrome (transmission)</term><term>Spike Glycoprotein, Coronavirus</term><term>Structure-Activity Relationship</term><term>Tropism</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (physiology)</term><term>Zoonoses</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Carboxypeptidases (métabolisme)</term><term>Données de séquences moléculaires</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (physiologie)</term><term>Humains</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (physiologie)</term><term>Relation structure-activité</term><term>Sites de fixation</term><term>Substitution d'acide aminé</term><term>Syndrome respiratoire aigu sévère (transmission)</term><term>Séquence d'acides aminés</term><term>Tropisme</term><term>Virus du SRAS ()</term><term>Virus du SRAS (pathogénicité)</term><term>Zoonoses</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Carboxypeptidases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Carboxypeptidases</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="physiologie" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term></keywords><keywords scheme="MESH" qualifier="transmission" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Amino Acid Substitution</term><term>Binding Sites</term><term>Humans</term><term>Molecular Sequence Data</term><term>Peptidyl-Dipeptidase A</term><term>Spike Glycoprotein, Coronavirus</term><term>Structure-Activity Relationship</term><term>Tropism</term><term>Zoonoses</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Données de séquences moléculaires</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Humains</term><term>Peptidyl-Dipeptidase A</term><term>Protéines de l'enveloppe virale</term><term>Relation structure-activité</term><term>Sites de fixation</term><term>Substitution d'acide aminé</term><term>Syndrome respiratoire aigu sévère</term><term>Séquence d'acides aminés</term><term>Tropisme</term><term>Virus du SRAS</term><term>Zoonoses</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome coronavirus (SARS-CoV) is a recently identified human coronavirus. The extremely high homology of the viral genomic sequences between the viruses isolated from human (huSARS-CoV) and those of palm civet origin (pcSARS-CoV) suggested possible palm civet-to-human transmission. Genetic analysis revealed that the spike (S) protein of pcSARS-CoV and huSARS-CoV was subjected to the strongest positive selection pressure during transmission, and there were six amino acid residues within the receptor-binding domain of the S protein being potentially important for SARS progression and tropism. Using the single-round infection assay, we found that a two-amino acid substitution (N479K/T487S) of a huSARS-CoV for those of pcSARS-CoV almost abolished its infection of human cells expressing the SARS-CoV receptor ACE2 but no effect upon the infection of mouse ACE2 cells. Although single substitution of these two residues had no effects on the infectivity of huSARS-CoV, these recombinant S proteins bound to human ACE2 with different levels of reduced affinity, and the two-amino acid-substituted S protein showed extremely low affinity. On the contrary, substitution of these two amino acid residues of pcSARS-CoV for those of huSRAS-CoV made pcSARS-CoV capable of infecting human ACE2-expressing cells. These results suggest that amino acid residues at position 479 and 487 of the S protein are important determinants for SARS-CoV tropism and animal-to-human transmission.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement><orgName><li>Université de Pékin</li></orgName></list><tree><noCountry><name sortKey="Deng, Fei" sort="Deng, Fei" uniqKey="Deng F" first="Fei" last="Deng">Fei Deng</name><name sortKey="Deng, Hong Kui" sort="Deng, Hong Kui" uniqKey="Deng H" first="Hong-Kui" last="Deng">Hong-Kui Deng</name><name sortKey="Ding, Ming Xiao" sort="Ding, Ming Xiao" uniqKey="Ding M" first="Ming-Xiao" last="Ding">Ming-Xiao Ding</name><name sortKey="Hao, Pei" sort="Hao, Pei" uniqKey="Hao P" first="Pei" last="Hao">Pei Hao</name><name sortKey="Hu, Zhi Hong" sort="Hu, Zhi Hong" uniqKey="Hu Z" first="Zhi-Hong" last="Hu">Zhi-Hong Hu</name><name sortKey="Jiang, Si Ming" sort="Jiang, Si Ming" uniqKey="Jiang S" first="Si-Ming" last="Jiang">Si-Ming Jiang</name><name sortKey="Liu, Yan Xia" sort="Liu, Yan Xia" uniqKey="Liu Y" first="Yan-Xia" last="Liu">Yan-Xia Liu</name><name sortKey="Luo, Min" sort="Luo, Min" uniqKey="Luo M" first="Min" last="Luo">Min Luo</name><name sortKey="Rao, Xi" sort="Rao, Xi" uniqKey="Rao X" first="Xi" last="Rao">Xi Rao</name><name sortKey="Song, Huai Dong" sort="Song, Huai Dong" uniqKey="Song H" first="Huai-Dong" last="Song">Huai-Dong Song</name><name sortKey="Song, Xi Jun" sort="Song, Xi Jun" uniqKey="Song X" first="Xi-Jun" last="Song">Xi-Jun Song</name><name sortKey="Wang, Han Zhong" sort="Wang, Han Zhong" uniqKey="Wang H" first="Han-Zhong" last="Wang">Han-Zhong Wang</name><name sortKey="Wang, Hua Lin" sort="Wang, Hua Lin" uniqKey="Wang H" first="Hua-Lin" last="Wang">Hua-Lin Wang</name><name sortKey="Wang, Pei Gang" sort="Wang, Pei Gang" uniqKey="Wang P" first="Pei-Gang" last="Wang">Pei-Gang Wang</name><name sortKey="Wang, Sheng Yue" sort="Wang, Sheng Yue" uniqKey="Wang S" first="Sheng-Yue" last="Wang">Sheng-Yue Wang</name><name sortKey="Zhao, Guo Ping" sort="Zhao, Guo Ping" uniqKey="Zhao G" first="Guo-Ping" last="Zhao">Guo-Ping Zhao</name><name sortKey="Zheng, Ai Hua" sort="Zheng, Ai Hua" uniqKey="Zheng A" first="Ai-Hua" last="Zheng">Ai-Hua Zheng</name><name sortKey="Zuo, Yu" sort="Zuo, Yu" uniqKey="Zuo Y" first="Yu" last="Zuo">Yu Zuo</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Qu, Xiu Xia" sort="Qu, Xiu Xia" uniqKey="Qu X" first="Xiu-Xia" last="Qu">Xiu-Xia Qu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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