RapamycinFungusV1, Main, Exploration, bibRecord, 000A30

Replication of the Shrimp Virus WSSV Depends on Glutamate-Driven Anaplerosis.

Identifieur interne : 000A30 ( Main/Exploration ); précédent : 000A29; suivant : 000A31

Replication of the Shrimp Virus WSSV Depends on Glutamate-Driven Anaplerosis.

Auteurs : Chun-Yuan Li [Taïwan] ; Yi-Jan Wang [Taïwan] ; Shiao-Wei Huang [Taïwan] ; Cheng-Shun Cheng [Taïwan] ; Han-Ching Wang [Taïwan]

Source :

PloS one [ 1932-6203 ] ; 2016.

RBID : pubmed:26751681

Descripteurs français

KwdFr :
- 4H-1-Benzopyran-4-ones (composition chimique), ARN double brin (génétique), ARN messager (métabolisme), Acide glutamique (métabolisme), Acides cétoglutariques (métabolisme), Animaux (MeSH), Aspartate aminotransferases (métabolisme), Cycle citrique (MeSH), Dosage génique (MeSH), Glutamate dehydrogenase (métabolisme), Glutaminase (métabolisme), Glutamine (métabolisme), Génome viral (MeSH), Hémocytes (cytologie), Hémocytes (métabolisme), Hémocytes (virologie), Hémolymphe (MeSH), Interférence par ARN (MeSH), Morpholines (composition chimique), Métabolomique (MeSH), Penaeidae (virologie), Phosphatidylinositol 3-kinases (métabolisme), Protéines proto-oncogènes c-akt (métabolisme), Réplication virale (MeSH), Sirolimus (composition chimique), Sérine-thréonine kinases TOR (métabolisme), Virus de type 1 du syndrome des taches blanches (physiologie).
MESH :
- composition chimique : 4H-1-Benzopyran-4-ones, Morpholines, Sirolimus.
- cytologie : Hémocytes.
- génétique : ARN double brin.
- métabolisme : ARN messager, Acide glutamique, Acides cétoglutariques, Aspartate aminotransferases, Glutamate dehydrogenase, Glutaminase, Glutamine, Hémocytes, Phosphatidylinositol 3-kinases, Protéines proto-oncogènes c-akt, Sérine-thréonine kinases TOR.
- physiologie : Virus de type 1 du syndrome des taches blanches.
- virologie : Hémocytes, Penaeidae.
- Animaux, Cycle citrique, Dosage génique, Génome viral, Hémolymphe, Interférence par ARN, Métabolomique, Réplication virale.

English descriptors

KwdEn :
- Animals (MeSH), Aspartate Aminotransferases (metabolism), Chromones (chemistry), Citric Acid Cycle (MeSH), Gene Dosage (MeSH), Genome, Viral (MeSH), Glutamate Dehydrogenase (metabolism), Glutamic Acid (metabolism), Glutaminase (metabolism), Glutamine (metabolism), Hemocytes (cytology), Hemocytes (metabolism), Hemocytes (virology), Hemolymph (MeSH), Ketoglutaric Acids (metabolism), Metabolomics (MeSH), Morpholines (chemistry), Penaeidae (virology), Phosphatidylinositol 3-Kinases (metabolism), Proto-Oncogene Proteins c-akt (metabolism), RNA Interference (MeSH), RNA, Double-Stranded (genetics), RNA, Messenger (metabolism), Sirolimus (chemistry), TOR Serine-Threonine Kinases (metabolism), Virus Replication (MeSH), White spot syndrome virus 1 (physiology).
MESH :
- chemical , chemistry : Chromones, Morpholines, Sirolimus.
- chemical , genetics : RNA, Double-Stranded.
- chemical , metabolism : Aspartate Aminotransferases, Glutamate Dehydrogenase, Glutamic Acid, Glutaminase, Glutamine, Ketoglutaric Acids, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, RNA, Messenger, TOR Serine-Threonine Kinases.
- cytology : Hemocytes.
- metabolism : Hemocytes.
- physiology : White spot syndrome virus 1.
- virology : Hemocytes, Penaeidae.
- Animals, Citric Acid Cycle, Gene Dosage, Genome, Viral, Hemolymph, Metabolomics, RNA Interference, Virus Replication.

Abstract

Infection with the white spot syndrome virus (WSSV) induces a metabolic shift in shrimp that resembles the "Warburg effect" in mammalian cells. This effect is triggered via activation of the PI3K-Akt-mTOR pathway, and it is usually accompanied by the activation of other metabolic pathways that provide energy and direct the flow of carbon and nitrogen. Here we show that unlike the glutamine metabolism (glutaminolysis) seen in most cancer cells to double deaminate glutamine to produce glutamate and the TCA cycle intermediate α-ketoglutarate (α-KG), at the WSSV genome replication stage (12 hpi), although glutaminase (GLS) expression was upregulated, only glutamate was taken up by the hemocytes of WSSV-infected shrimp. At the same time, we observed an increase in the activity of the two enzymes that convert glutamate to α-KG, glutamate dehydrogenase (GDH) and aspartate aminotransferase (ASAT). α-ketoglutarate concentration was also increased. A series of inhibition experiments suggested that the up-regulation of GDH is regulated by mTORC2, and that the PI3K-mTORC1 pathway is not involved. Suppression of GDH and ASAT by dsRNA silencing showed that both of these enzymes are important for WSSV replication. In GDH-silenced shrimp, direct replenishment of α-KG rescued both ATP production and WSSV replication. From these results, we propose a model of glutamate-driven anaplerosis that fuels the TCA cycle via α-KG and ultimately supports WSSV replication.

DOI: 10.1371/journal.pone.0146902
PubMed: 26751681
PubMed Central: PMC4709008

Affiliations:

Taïwan

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000B24
to stream Main, to step Curation: 000B24

Le document en format XML

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<term>Aspartate Aminotransferases (metabolism)</term>
<term>Chromones (chemistry)</term>
<term>Citric Acid Cycle (MeSH)</term>
<term>Gene Dosage (MeSH)</term>
<term>Genome, Viral (MeSH)</term>
<term>Glutamate Dehydrogenase (metabolism)</term>
<term>Glutamic Acid (metabolism)</term>
<term>Glutaminase (metabolism)</term>
<term>Glutamine (metabolism)</term>
<term>Hemocytes (cytology)</term>
<term>Hemocytes (metabolism)</term>
<term>Hemocytes (virology)</term>
<term>Hemolymph (MeSH)</term>
<term>Ketoglutaric Acids (metabolism)</term>
<term>Metabolomics (MeSH)</term>
<term>Morpholines (chemistry)</term>
<term>Penaeidae (virology)</term>
<term>Phosphatidylinositol 3-Kinases (metabolism)</term>
<term>Proto-Oncogene Proteins c-akt (metabolism)</term>
<term>RNA Interference (MeSH)</term>
<term>RNA, Double-Stranded (genetics)</term>
<term>RNA, Messenger (metabolism)</term>
<term>Sirolimus (chemistry)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>Virus Replication (MeSH)</term>
<term>White spot syndrome virus 1 (physiology)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>4H-1-Benzopyran-4-ones (composition chimique)</term>
<term>ARN double brin (génétique)</term>
<term>ARN messager (métabolisme)</term>
<term>Acide glutamique (métabolisme)</term>
<term>Acides cétoglutariques (métabolisme)</term>
<term>Animaux (MeSH)</term>
<term>Aspartate aminotransferases (métabolisme)</term>
<term>Cycle citrique (MeSH)</term>
<term>Dosage génique (MeSH)</term>
<term>Glutamate dehydrogenase (métabolisme)</term>
<term>Glutaminase (métabolisme)</term>
<term>Glutamine (métabolisme)</term>
<term>Génome viral (MeSH)</term>
<term>Hémocytes (cytologie)</term>
<term>Hémocytes (métabolisme)</term>
<term>Hémocytes (virologie)</term>
<term>Hémolymphe (MeSH)</term>
<term>Interférence par ARN (MeSH)</term>
<term>Morpholines (composition chimique)</term>
<term>Métabolomique (MeSH)</term>
<term>Penaeidae (virologie)</term>
<term>Phosphatidylinositol 3-kinases (métabolisme)</term>
<term>Protéines proto-oncogènes c-akt (métabolisme)</term>
<term>Réplication virale (MeSH)</term>
<term>Sirolimus (composition chimique)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Virus de type 1 du syndrome des taches blanches (physiologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Chromones</term>
<term>Morpholines</term>
<term>Sirolimus</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Double-Stranded</term>
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<term>Glutamic Acid</term>
<term>Glutaminase</term>
<term>Glutamine</term>
<term>Ketoglutaric Acids</term>
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<term>TOR Serine-Threonine Kinases</term>
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<term>Acide glutamique</term>
<term>Acides cétoglutariques</term>
<term>Aspartate aminotransferases</term>
<term>Glutamate dehydrogenase</term>
<term>Glutaminase</term>
<term>Glutamine</term>
<term>Hémocytes</term>
<term>Phosphatidylinositol 3-kinases</term>
<term>Protéines proto-oncogènes c-akt</term>
<term>Sérine-thréonine kinases TOR</term>
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<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus de type 1 du syndrome des taches blanches</term>
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<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>White spot syndrome virus 1</term>
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<term>Genome, Viral</term>
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<term>Génome viral</term>
<term>Hémolymphe</term>
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<front><div type="abstract" xml:lang="en">Infection with the white spot syndrome virus (WSSV) induces a metabolic shift in shrimp that resembles the "Warburg effect" in mammalian cells. This effect is triggered via activation of the PI3K-Akt-mTOR pathway, and it is usually accompanied by the activation of other metabolic pathways that provide energy and direct the flow of carbon and nitrogen. Here we show that unlike the glutamine metabolism (glutaminolysis) seen in most cancer cells to double deaminate glutamine to produce glutamate and the TCA cycle intermediate α-ketoglutarate (α-KG), at the WSSV genome replication stage (12 hpi), although glutaminase (GLS) expression was upregulated, only glutamate was taken up by the hemocytes of WSSV-infected shrimp. At the same time, we observed an increase in the activity of the two enzymes that convert glutamate to α-KG, glutamate dehydrogenase (GDH) and aspartate aminotransferase (ASAT). α-ketoglutarate concentration was also increased. A series of inhibition experiments suggested that the up-regulation of GDH is regulated by mTORC2, and that the PI3K-mTORC1 pathway is not involved. Suppression of GDH and ASAT by dsRNA silencing showed that both of these enzymes are important for WSSV replication. In GDH-silenced shrimp, direct replenishment of α-KG rescued both ATP production and WSSV replication. From these results, we propose a model of glutamate-driven anaplerosis that fuels the TCA cycle via α-KG and ultimately supports WSSV replication. </div>
</front>
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<Abstract><AbstractText>Infection with the white spot syndrome virus (WSSV) induces a metabolic shift in shrimp that resembles the "Warburg effect" in mammalian cells. This effect is triggered via activation of the PI3K-Akt-mTOR pathway, and it is usually accompanied by the activation of other metabolic pathways that provide energy and direct the flow of carbon and nitrogen. Here we show that unlike the glutamine metabolism (glutaminolysis) seen in most cancer cells to double deaminate glutamine to produce glutamate and the TCA cycle intermediate α-ketoglutarate (α-KG), at the WSSV genome replication stage (12 hpi), although glutaminase (GLS) expression was upregulated, only glutamate was taken up by the hemocytes of WSSV-infected shrimp. At the same time, we observed an increase in the activity of the two enzymes that convert glutamate to α-KG, glutamate dehydrogenase (GDH) and aspartate aminotransferase (ASAT). α-ketoglutarate concentration was also increased. A series of inhibition experiments suggested that the up-regulation of GDH is regulated by mTORC2, and that the PI3K-mTORC1 pathway is not involved. Suppression of GDH and ASAT by dsRNA silencing showed that both of these enzymes are important for WSSV replication. In GDH-silenced shrimp, direct replenishment of α-KG rescued both ATP production and WSSV replication. From these results, we propose a model of glutamate-driven anaplerosis that fuels the TCA cycle via α-KG and ultimately supports WSSV replication. </AbstractText>
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<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Li</LastName>
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<AffiliationInfo><Affiliation>Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.</Affiliation>
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<AffiliationInfo><Affiliation>Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan.</Affiliation>
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<Author ValidYN="Y"><LastName>Cheng</LastName>
<ForeName>Cheng-Shun</ForeName>
<Initials>CS</Initials>
<AffiliationInfo><Affiliation>Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Han-Ching</ForeName>
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<AffiliationInfo><Affiliation>Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.</Affiliation>
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	Serveur d'exploration sur la rapamycine et les champignons
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Replication of the Shrimp Virus WSSV Depends on Glutamate-Driven Anaplerosis.

Replication of the Shrimp Virus WSSV Depends on Glutamate-Driven Anaplerosis.

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