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Syncytia generated by hemagglutinin-neuraminidase and fusion proteins of virulent Newcastle disease virus induce complete autophagy by activating AMPK-mTORC1-ULK1 signaling>.

Identifieur interne : 000224 ( Main/Exploration ); précédent : 000223; suivant : 000225

Syncytia generated by hemagglutinin-neuraminidase and fusion proteins of virulent Newcastle disease virus induce complete autophagy by activating AMPK-mTORC1-ULK1 signaling>.

Auteurs : Shanhui Ren [République populaire de Chine] ; Zaib Ur Rehman [République populaire de Chine] ; Mengyu Shi [République populaire de Chine] ; Bin Yang [République populaire de Chine] ; Yurong Qu [République populaire de Chine] ; Xiao Feng Yang [République populaire de Chine] ; Qi Shao [République populaire de Chine] ; Chunchun Meng [République populaire de Chine] ; Zengqi Yang [République populaire de Chine] ; Xiaolong Gao [République populaire de Chine] ; Yingjie Sun [République populaire de Chine] ; Chan Ding [République populaire de Chine]

Source :

RBID : pubmed:30658866

Descripteurs français

English descriptors

Abstract

Autophagy triggered by glycoprotein-mediated membrane fusion has been reported for several paramyxoviruses. However, the function of HN and F glycoproteins of NDV and their role in autophagy induction have not been studied. Here, we found that co-transfection of HN and F of virulent NDV rapidly induced syncytium formation and triggered a steady state autophagy flux in adenocarcinomic human alveolar basal epithelial (A549) cells and chicken embryo fibroblast (DF-1) cells. Furthermore, we clearly identified that F and HN synergistically induced autophagosome fusion with lysosomes for subsequent degradation. The seven cleavage site mutations of F significantly decreased the autophagy induction, compared with those of wildtype virulent F. RNAi and pharmacological experiments suggested that autophagy benefitted membrane fusion and syncytium formation induced by F and HN of NDV. Activated F1 co-operated with HN to stimulate AMPK kinase and downstream ULK1 activation to suppress mTORC1 signaling. Our data described the synergistic role of HN and F in the induction of completed autophagic flux through the activation of AMPK- mTORC1- ULK1 pathway.

DOI: 10.1016/j.vetmic.2019.01.002
PubMed: 30658866


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<name sortKey="Ding, Chan" sort="Ding, Chan" uniqKey="Ding C" first="Chan" last="Ding">Chan Ding</name>
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<name sortKey="Shao, Qi" sort="Shao, Qi" uniqKey="Shao Q" first="Qi" last="Shao">Qi Shao</name>
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<wicri:regionArea>Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, 200241</wicri:regionArea>
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<name sortKey="Meng, Chunchun" sort="Meng, Chunchun" uniqKey="Meng C" first="Chunchun" last="Meng">Chunchun Meng</name>
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<nlm:affiliation>Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, 200241, PR China.</nlm:affiliation>
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<name sortKey="Yang, Zengqi" sort="Yang, Zengqi" uniqKey="Yang Z" first="Zengqi" last="Yang">Zengqi Yang</name>
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<nlm:affiliation>College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi</wicri:regionArea>
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<name sortKey="Gao, Xiaolong" sort="Gao, Xiaolong" uniqKey="Gao X" first="Xiaolong" last="Gao">Xiaolong Gao</name>
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<wicri:regionArea>College of Agriculture and Animal Husbandary, Qinghai University, Xining, Qinghai 810016</wicri:regionArea>
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<country xml:lang="fr">République populaire de Chine</country>
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<wicri:noRegion>200241</wicri:noRegion>
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<name sortKey="Ding, Chan" sort="Ding, Chan" uniqKey="Ding C" first="Chan" last="Ding">Chan Ding</name>
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<nlm:affiliation>Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, 200241, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yang Zhou, 225009, PR China. Electronic address: shoveldeen@shvri.ac.cn.</nlm:affiliation>
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<term>A549 Cells (MeSH)</term>
<term>Animals (MeSH)</term>
<term>Autophagosomes (metabolism)</term>
<term>Autophagosomes (virology)</term>
<term>Autophagy (MeSH)</term>
<term>Cell Line (MeSH)</term>
<term>Chickens (MeSH)</term>
<term>Fibroblasts (virology)</term>
<term>Giant Cells (metabolism)</term>
<term>Giant Cells (virology)</term>
<term>Hemagglutinins, Viral (genetics)</term>
<term>Humans (MeSH)</term>
<term>Intracellular Signaling Peptides and Proteins (MeSH)</term>
<term>Lysosomes (metabolism)</term>
<term>Lysosomes (virology)</term>
<term>Mechanistic Target of Rapamycin Complex 1 (metabolism)</term>
<term>Mutation (MeSH)</term>
<term>Neuraminidase (genetics)</term>
<term>Newcastle Disease (pathology)</term>
<term>Newcastle disease virus (genetics)</term>
<term>Newcastle disease virus (pathogenicity)</term>
<term>Plasmids (genetics)</term>
<term>Protein Kinases (metabolism)</term>
<term>RNA, Small Interfering (MeSH)</term>
<term>Signal Transduction (MeSH)</term>
<term>Transfection (MeSH)</term>
<term>Viral Fusion Proteins (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux (MeSH)</term>
<term>Autophagie (MeSH)</term>
<term>Autophagosomes (métabolisme)</term>
<term>Autophagosomes (virologie)</term>
<term>Cellules A549 (MeSH)</term>
<term>Cellules géantes (métabolisme)</term>
<term>Cellules géantes (virologie)</term>
<term>Complexe-1 cible mécanistique de la rapamycine (métabolisme)</term>
<term>Fibroblastes (virologie)</term>
<term>Humains (MeSH)</term>
<term>Hémagglutinines virales (génétique)</term>
<term>Lignée cellulaire (MeSH)</term>
<term>Lysosomes (métabolisme)</term>
<term>Lysosomes (virologie)</term>
<term>Maladie de Newcastle (anatomopathologie)</term>
<term>Mutation (MeSH)</term>
<term>Petit ARN interférent (MeSH)</term>
<term>Plasmides (génétique)</term>
<term>Poulets (MeSH)</term>
<term>Protein kinases (métabolisme)</term>
<term>Protéines de fusion virale (génétique)</term>
<term>Protéines et peptides de signalisation intracellulaire (MeSH)</term>
<term>Sialidase (génétique)</term>
<term>Transduction du signal (MeSH)</term>
<term>Transfection (MeSH)</term>
<term>Virus de la maladie de Newcastle (génétique)</term>
<term>Virus de la maladie de Newcastle (pathogénicité)</term>
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<term>Hemagglutinins, Viral</term>
<term>Neuraminidase</term>
<term>Viral Fusion Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Maladie de Newcastle</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Newcastle disease virus</term>
<term>Plasmids</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Hémagglutinines virales</term>
<term>Plasmides</term>
<term>Protéines de fusion virale</term>
<term>Sialidase</term>
<term>Virus de la maladie de Newcastle</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Autophagosomes</term>
<term>Giant Cells</term>
<term>Lysosomes</term>
<term>Mechanistic Target of Rapamycin Complex 1</term>
<term>Protein Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Autophagosomes</term>
<term>Cellules géantes</term>
<term>Complexe-1 cible mécanistique de la rapamycine</term>
<term>Lysosomes</term>
<term>Protein kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en">
<term>Newcastle disease virus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr">
<term>Virus de la maladie de Newcastle</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Newcastle Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Autophagosomes</term>
<term>Cellules géantes</term>
<term>Fibroblastes</term>
<term>Lysosomes</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Autophagosomes</term>
<term>Fibroblasts</term>
<term>Giant Cells</term>
<term>Lysosomes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>A549 Cells</term>
<term>Animals</term>
<term>Autophagy</term>
<term>Cell Line</term>
<term>Chickens</term>
<term>Humans</term>
<term>Intracellular Signaling Peptides and Proteins</term>
<term>Mutation</term>
<term>RNA, Small Interfering</term>
<term>Signal Transduction</term>
<term>Transfection</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Autophagie</term>
<term>Cellules A549</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Mutation</term>
<term>Petit ARN interférent</term>
<term>Poulets</term>
<term>Protéines et peptides de signalisation intracellulaire</term>
<term>Transduction du signal</term>
<term>Transfection</term>
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<div type="abstract" xml:lang="en">Autophagy triggered by glycoprotein-mediated membrane fusion has been reported for several paramyxoviruses. However, the function of HN and F glycoproteins of NDV and their role in autophagy induction have not been studied. Here, we found that co-transfection of HN and F of virulent NDV rapidly induced syncytium formation and triggered a steady state autophagy flux in adenocarcinomic human alveolar basal epithelial (A549) cells and chicken embryo fibroblast (DF-1) cells. Furthermore, we clearly identified that F and HN synergistically induced autophagosome fusion with lysosomes for subsequent degradation. The seven cleavage site mutations of F significantly decreased the autophagy induction, compared with those of wildtype virulent F. RNAi and pharmacological experiments suggested that autophagy benefitted membrane fusion and syncytium formation induced by F and HN of NDV. Activated F
<sub>1</sub>
co-operated with HN to stimulate AMPK kinase and downstream ULK1 activation to suppress mTORC1 signaling. Our data described the synergistic role of HN and F in the induction of completed autophagic flux through the activation of AMPK- mTORC1- ULK1 pathway.</div>
</front>
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<DateCompleted>
<Year>2019</Year>
<Month>04</Month>
<Day>19</Day>
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<Volume>230</Volume>
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<Year>2019</Year>
<Month>Mar</Month>
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<Title>Veterinary microbiology</Title>
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<ArticleTitle>Syncytia generated by hemagglutinin-neuraminidase and fusion proteins of virulent Newcastle disease virus induce complete autophagy by activating AMPK-mTORC1-ULK1 signaling>.</ArticleTitle>
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<Abstract>
<AbstractText>Autophagy triggered by glycoprotein-mediated membrane fusion has been reported for several paramyxoviruses. However, the function of HN and F glycoproteins of NDV and their role in autophagy induction have not been studied. Here, we found that co-transfection of HN and F of virulent NDV rapidly induced syncytium formation and triggered a steady state autophagy flux in adenocarcinomic human alveolar basal epithelial (A549) cells and chicken embryo fibroblast (DF-1) cells. Furthermore, we clearly identified that F and HN synergistically induced autophagosome fusion with lysosomes for subsequent degradation. The seven cleavage site mutations of F significantly decreased the autophagy induction, compared with those of wildtype virulent F. RNAi and pharmacological experiments suggested that autophagy benefitted membrane fusion and syncytium formation induced by F and HN of NDV. Activated F
<sub>1</sub>
co-operated with HN to stimulate AMPK kinase and downstream ULK1 activation to suppress mTORC1 signaling. Our data described the synergistic role of HN and F in the induction of completed autophagic flux through the activation of AMPK- mTORC1- ULK1 pathway.</AbstractText>
<CopyrightInformation>Copyright © 2019 Elsevier B.V. All rights reserved.</CopyrightInformation>
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<LastName>Ren</LastName>
<ForeName>Shanhui</ForeName>
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<Affiliation>Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, 200241, PR China.</Affiliation>
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