Phosphatidylinositol 4-kinase IIIβ is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry.
Identifieur interne : 001C86 ( Main/Exploration ); précédent : 001C85; suivant : 001C87Phosphatidylinositol 4-kinase IIIβ is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry.
Auteurs : Ning Yang [République populaire de Chine] ; Ping Ma ; Jianshe Lang ; Yanli Zhang ; Jiejie Deng ; Xiangwu Ju ; Gongyi Zhang ; Chengyu JiangSource :
- The Journal of biological chemistry [ 1083-351X ] ; 2012.
Descripteurs français
- KwdFr :
- Animaux, Antienzymes (), Antienzymes (pharmacologie), Antigènes mineurs d'histocompatibilité, Cellules HEK293, Humains, Lipides membranaires (métabolisme), Phosphotransferases (Alcohol Group Acceptor) (antagonistes et inhibiteurs), Phosphotransferases (Alcohol Group Acceptor) (métabolisme), Pénétration virale, Syndrome respiratoire aigu sévère (métabolisme), Syndrome respiratoire aigu sévère (traitement médicamenteux), Virion (métabolisme), Virus du SRAS (métabolisme).
- MESH :
- antagonistes et inhibiteurs : Phosphotransferases (Alcohol Group Acceptor).
- métabolisme : Lipides membranaires, Phosphotransferases (Alcohol Group Acceptor), Syndrome respiratoire aigu sévère, Virion, Virus du SRAS.
- pharmacologie : Antienzymes.
- traitement médicamenteux : Syndrome respiratoire aigu sévère.
- Animaux, Antienzymes, Antigènes mineurs d'histocompatibilité, Cellules HEK293, Humains, Pénétration virale.
English descriptors
- KwdEn :
- Animals, Chlorocebus aethiops, Enzyme Inhibitors (chemistry), Enzyme Inhibitors (pharmacology), HEK293 Cells, Humans, Membrane Lipids (metabolism), Minor Histocompatibility Antigens, Phosphotransferases (Alcohol Group Acceptor) (antagonists & inhibitors), Phosphotransferases (Alcohol Group Acceptor) (metabolism), SARS Virus (metabolism), Severe Acute Respiratory Syndrome (drug therapy), Severe Acute Respiratory Syndrome (metabolism), Virion (metabolism), Virus Internalization.
- MESH :
- chemical , antagonists & inhibitors : Phosphotransferases (Alcohol Group Acceptor).
- chemical , chemistry : Enzyme Inhibitors.
- chemical , metabolism : Membrane Lipids, Phosphotransferases (Alcohol Group Acceptor).
- chemical , pharmacology : Enzyme Inhibitors.
- drug therapy : Severe Acute Respiratory Syndrome.
- metabolism : SARS Virus, Severe Acute Respiratory Syndrome, Virion.
- Animals, Chlorocebus aethiops, HEK293 Cells, Humans, Minor Histocompatibility Antigens, Virus Internalization.
Abstract
Phosphatidylinositol kinases (PI kinases) play an important role in the life cycle of several viruses after infection. Using gene knockdown technology, we demonstrate that phosphatidylinositol 4-kinase IIIβ (PI4KB) is required for cellular entry by pseudoviruses bearing the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike protein and that the cell entry mediated by SARS-CoV spike protein is strongly inhibited by knockdown of PI4KB. Consistent with this observation, pharmacological inhibitors of PI4KB blocked entry of SARS pseudovirions. Further research suggested that PI4P plays an essential role in SARS-CoV spike-mediated entry, which is regulated by the PI4P lipid microenvironment. We further demonstrate that PI4KB does not affect virus entry at the SARS-CoV S-ACE2 binding interface or at the stage of virus internalization but rather at or before virus fusion. Taken together, these results indicate a new function for PI4KB and suggest a new drug target for preventing SARS-CoV infection.
DOI: 10.1074/jbc.M111.312561
PubMed: 22253445
Affiliations:
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Le document en format XML
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spike-mediated cell entry.</title><author><name sortKey="Yang, Ning" sort="Yang, Ning" uniqKey="Yang N" first="Ning" last="Yang">Ning Yang</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College, Tsinghua University, Chinese Academy of Medical Sciences, Beijing 100005, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College, Tsinghua University, Chinese Academy of Medical Sciences, Beijing 100005</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Ma, Ping" sort="Ma, Ping" uniqKey="Ma P" first="Ping" last="Ma">Ping Ma</name></author><author><name sortKey="Lang, Jianshe" sort="Lang, Jianshe" uniqKey="Lang J" first="Jianshe" last="Lang">Jianshe Lang</name></author><author><name sortKey="Zhang, Yanli" sort="Zhang, Yanli" uniqKey="Zhang Y" first="Yanli" last="Zhang">Yanli Zhang</name></author><author><name sortKey="Deng, Jiejie" sort="Deng, Jiejie" uniqKey="Deng J" first="Jiejie" last="Deng">Jiejie Deng</name></author><author><name sortKey="Ju, Xiangwu" sort="Ju, Xiangwu" uniqKey="Ju X" first="Xiangwu" last="Ju">Xiangwu Ju</name></author><author><name sortKey="Zhang, Gongyi" sort="Zhang, Gongyi" uniqKey="Zhang G" first="Gongyi" last="Zhang">Gongyi Zhang</name></author><author><name sortKey="Jiang, Chengyu" sort="Jiang, Chengyu" uniqKey="Jiang C" first="Chengyu" last="Jiang">Chengyu Jiang</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" 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(antagonistes et inhibiteurs)</term><term>Phosphotransferases (Alcohol Group Acceptor) (métabolisme)</term><term>Pénétration virale</term><term>Syndrome respiratoire aigu sévère (métabolisme)</term><term>Syndrome respiratoire aigu sévère (traitement médicamenteux)</term><term>Virion (métabolisme)</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Phosphotransferases (Alcohol Group Acceptor)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Enzyme Inhibitors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Membrane Lipids</term><term>Phosphotransferases (Alcohol Group Acceptor)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Enzyme Inhibitors</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Phosphotransferases (Alcohol Group Acceptor)</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term><term>Virion</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Lipides membranaires</term><term>Phosphotransferases (Alcohol Group Acceptor)</term><term>Syndrome respiratoire aigu sévère</term><term>Virion</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antienzymes</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>HEK293 Cells</term><term>Humans</term><term>Minor Histocompatibility Antigens</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Antienzymes</term><term>Antigènes mineurs d'histocompatibilité</term><term>Cellules HEK293</term><term>Humains</term><term>Pénétration virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Phosphatidylinositol kinases (PI kinases) play an important role in the life cycle of several viruses after infection. Using gene knockdown technology, we demonstrate that phosphatidylinositol 4-kinase IIIβ (PI4KB) is required for cellular entry by pseudoviruses bearing the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike protein and that the cell entry mediated by SARS-CoV spike protein is strongly inhibited by knockdown of PI4KB. Consistent with this observation, pharmacological inhibitors of PI4KB blocked entry of SARS pseudovirions. Further research suggested that PI4P plays an essential role in SARS-CoV spike-mediated entry, which is regulated by the PI4P lipid microenvironment. We further demonstrate that PI4KB does not affect virus entry at the SARS-CoV S-ACE2 binding interface or at the stage of virus internalization but rather at or before virus fusion. Taken together, these results indicate a new function for PI4KB and suggest a new drug target for preventing SARS-CoV infection.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><noCountry><name sortKey="Deng, Jiejie" sort="Deng, Jiejie" uniqKey="Deng J" first="Jiejie" last="Deng">Jiejie Deng</name><name sortKey="Jiang, Chengyu" sort="Jiang, Chengyu" uniqKey="Jiang C" first="Chengyu" last="Jiang">Chengyu Jiang</name><name sortKey="Ju, Xiangwu" sort="Ju, Xiangwu" uniqKey="Ju X" first="Xiangwu" last="Ju">Xiangwu Ju</name><name sortKey="Lang, Jianshe" sort="Lang, Jianshe" uniqKey="Lang J" first="Jianshe" last="Lang">Jianshe Lang</name><name sortKey="Ma, Ping" sort="Ma, Ping" uniqKey="Ma P" first="Ping" last="Ma">Ping Ma</name><name sortKey="Zhang, Gongyi" sort="Zhang, Gongyi" uniqKey="Zhang G" first="Gongyi" last="Zhang">Gongyi Zhang</name><name sortKey="Zhang, Yanli" sort="Zhang, Yanli" uniqKey="Zhang Y" first="Yanli" last="Zhang">Yanli Zhang</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Yang, Ning" sort="Yang, Ning" uniqKey="Yang N" first="Ning" last="Yang">Ning Yang</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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