Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors.
Identifieur interne : 000D02 ( Main/Exploration ); précédent : 000D01; suivant : 000D03Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors.
Auteurs : Jeanne M. Sisk [États-Unis] ; Matthew B. Frieman [États-Unis] ; Carolyn E. Machamer [États-Unis]Source :
- The Journal of general virology [ 1465-2099 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (pharmacologie), Benzamides (pharmacologie), Cellules Vero, Endosomes (virologie), Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (métabolisme), Inhibiteurs de protéines kinases (pharmacologie), Membrane cellulaire, Mésylate d'imatinib (pharmacologie), Protéines proto-oncogènes c-abl (antagonistes et inhibiteurs), Pyrimidines (pharmacologie), Pénétration virale, Réplication virale, Virus de la bronchite infectieuse (génétique), Virus de la bronchite infectieuse (métabolisme).
- MESH :
- antagonistes et inhibiteurs : Protéines proto-oncogènes c-abl.
- génétique : Glycoprotéine de spicule des coronavirus, Virus de la bronchite infectieuse.
- métabolisme : Glycoprotéine de spicule des coronavirus, Virus de la bronchite infectieuse.
- pharmacologie : Antiviraux, Benzamides, Inhibiteurs de protéines kinases, Mésylate d'imatinib, Pyrimidines.
- virologie : Endosomes.
- Animaux, Cellules Vero, Membrane cellulaire, Pénétration virale, Réplication virale.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (pharmacology), Benzamides (pharmacology), Cell Membrane, Chlorocebus aethiops, Endosomes (virology), Imatinib Mesylate (pharmacology), Infectious bronchitis virus (genetics), Infectious bronchitis virus (metabolism), Protein Kinase Inhibitors (pharmacology), Proto-Oncogene Proteins c-abl (antagonists & inhibitors), Pyrimidines (pharmacology), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (metabolism), Vero Cells, Virus Internalization, Virus Replication.
- MESH :
- chemical , antagonists & inhibitors : Proto-Oncogene Proteins c-abl.
- chemical , genetics : Spike Glycoprotein, Coronavirus.
- chemical , metabolism : Spike Glycoprotein, Coronavirus.
- chemical , pharmacology : Antiviral Agents, Benzamides, Imatinib Mesylate, Protein Kinase Inhibitors, Pyrimidines.
- genetics : Infectious bronchitis virus.
- metabolism : Infectious bronchitis virus.
- virology : Endosomes.
- Animals, Cell Membrane, Chlorocebus aethiops, Vero Cells, Virus Internalization, Virus Replication.
Abstract
Enveloped viruses gain entry into host cells by fusing with cellular membranes, a step that is required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes, depending on the cell or tissue type. The virus spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abelson (Abl) kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titres and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions. SARS-CoV and MERS-CoV are classified as BSL-3 viruses, which makes experimentation into the cellular mechanisms involved in infection more challenging. Here, we use IBV, a BSL-2 virus, as a model for studying the role of Abl kinase activity during coronavirus infection. We found that imatinib and two specific Abl kinase inhibitors, GNF2 and GNF5, reduce IBV titres by blocking the first round of virus infection. Additionally, all three drugs prevented IBV S-induced syncytia formation prior to the hemifusion step. Our results indicate that membrane fusion (both virus-cell and cell-cell) is blocked in the presence of Abl kinase inhibitors. Studying the effects of Abl kinase inhibitors on IBV will be useful in identifying the host cell pathways required for coronavirus infection. This will provide an insight into possible therapeutic targets to treat infections by current as well as newly emerging coronaviruses.
DOI: 10.1099/jgv.0.001047
PubMed: 29557770
Affiliations:
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Le document en format XML
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Sisk</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B" last="Frieman">Matthew B. Frieman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Machamer, Carolyn E" sort="Machamer, Carolyn E" uniqKey="Machamer C" first="Carolyn E" last="Machamer">Carolyn E. Machamer</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of general virology</title><idno type="eISSN">1465-2099</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (pharmacology)</term><term>Benzamides (pharmacology)</term><term>Cell Membrane</term><term>Chlorocebus aethiops</term><term>Endosomes (virology)</term><term>Imatinib Mesylate (pharmacology)</term><term>Infectious bronchitis virus (genetics)</term><term>Infectious bronchitis virus (metabolism)</term><term>Protein Kinase Inhibitors (pharmacology)</term><term>Proto-Oncogene Proteins c-abl (antagonists & inhibitors)</term><term>Pyrimidines (pharmacology)</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (metabolism)</term><term>Vero Cells</term><term>Virus Internalization</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux (pharmacologie)</term><term>Benzamides (pharmacologie)</term><term>Cellules Vero</term><term>Endosomes (virologie)</term><term>Glycoprotéine de spicule des coronavirus (génétique)</term><term>Glycoprotéine de spicule des coronavirus (métabolisme)</term><term>Inhibiteurs de protéines kinases (pharmacologie)</term><term>Membrane cellulaire</term><term>Mésylate d'imatinib (pharmacologie)</term><term>Protéines proto-oncogènes c-abl (antagonistes et inhibiteurs)</term><term>Pyrimidines (pharmacologie)</term><term>Pénétration virale</term><term>Réplication virale</term><term>Virus de la bronchite infectieuse (génétique)</term><term>Virus de la bronchite infectieuse (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Proto-Oncogene Proteins c-abl</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Benzamides</term><term>Imatinib Mesylate</term><term>Protein Kinase Inhibitors</term><term>Pyrimidines</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines proto-oncogènes c-abl</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Infectious bronchitis virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term><term>Virus de la bronchite infectieuse</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Infectious bronchitis virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term><term>Virus de la bronchite infectieuse</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Benzamides</term><term>Inhibiteurs de protéines kinases</term><term>Mésylate d'imatinib</term><term>Pyrimidines</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Endosomes</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Endosomes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Membrane</term><term>Chlorocebus aethiops</term><term>Vero Cells</term><term>Virus Internalization</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Membrane cellulaire</term><term>Pénétration virale</term><term>Réplication virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Enveloped viruses gain entry into host cells by fusing with cellular membranes, a step that is required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes, depending on the cell or tissue type. The virus spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abelson (Abl) kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titres and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions. SARS-CoV and MERS-CoV are classified as BSL-3 viruses, which makes experimentation into the cellular mechanisms involved in infection more challenging. Here, we use IBV, a BSL-2 virus, as a model for studying the role of Abl kinase activity during coronavirus infection. We found that imatinib and two specific Abl kinase inhibitors, GNF2 and GNF5, reduce IBV titres by blocking the first round of virus infection. Additionally, all three drugs prevented IBV S-induced syncytia formation prior to the hemifusion step. Our results indicate that membrane fusion (both virus-cell and cell-cell) is blocked in the presence of Abl kinase inhibitors. Studying the effects of Abl kinase inhibitors on IBV will be useful in identifying the host cell pathways required for coronavirus infection. This will provide an insight into possible therapeutic targets to treat infections by current as well as newly emerging coronaviruses.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Sisk, Jeanne M" sort="Sisk, Jeanne M" uniqKey="Sisk J" first="Jeanne M" last="Sisk">Jeanne M. Sisk</name></region><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B" last="Frieman">Matthew B. Frieman</name><name sortKey="Machamer, Carolyn E" sort="Machamer, Carolyn E" uniqKey="Machamer C" first="Carolyn E" last="Machamer">Carolyn E. Machamer</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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