An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway.

In this study, we used a systems biology approach to investigate changes in the proteome and metabolome of shrimp hemocytes infected by the invertebrate virus WSSV (white spot syndrome virus) at the viral genome replication stage (12 hpi) and the late stage (24 hpi). At 12 hpi, but not at 24 hpi, th...

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Autores principales: Mei-An Su, Yun-Tzu Huang, I-Tung Chen, Der-Yen Lee, Yun-Chieh Hsieh, Chun-Yuan Li, Tze Hann Ng, Suh-Yuen Liang, Shu-Yu Lin, Shiao-Wei Huang, Yi-An Chiang, Hon-Tsen Yu, Kay-Hooi Khoo, Geen-Dong Chang, Chu-Fang Lo, Han-Ching Wang
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Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/bc700c6a000f4d76beffb3323cb67691
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spelling oai:doaj.org-article:bc700c6a000f4d76beffb3323cb676912021-11-11T06:06:10ZAn invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway.1553-73661553-737410.1371/journal.ppat.1004196https://doaj.org/article/bc700c6a000f4d76beffb3323cb676912014-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24945378/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374In this study, we used a systems biology approach to investigate changes in the proteome and metabolome of shrimp hemocytes infected by the invertebrate virus WSSV (white spot syndrome virus) at the viral genome replication stage (12 hpi) and the late stage (24 hpi). At 12 hpi, but not at 24 hpi, there was significant up-regulation of the markers of several metabolic pathways associated with the vertebrate Warburg effect (or aerobic glycolysis), including glycolysis, the pentose phosphate pathway, nucleotide biosynthesis, glutaminolysis and amino acid biosynthesis. We show that the PI3K-Akt-mTOR pathway was of central importance in triggering this WSSV-induced Warburg effect. Although dsRNA silencing of the mTORC1 activator Rheb had only a relatively minor impact on WSSV replication, in vivo chemical inhibition of Akt, mTORC1 and mTORC2 suppressed the WSSV-induced Warburg effect and reduced both WSSV gene expression and viral genome replication. When the Warburg effect was suppressed by pretreatment with the mTOR inhibitor Torin 1, even the subsequent up-regulation of the TCA cycle was insufficient to satisfy the virus's requirements for energy and macromolecular precursors. The WSSV-induced Warburg effect therefore appears to be essential for successful viral replication.Mei-An SuYun-Tzu HuangI-Tung ChenDer-Yen LeeYun-Chieh HsiehChun-Yuan LiTze Hann NgSuh-Yuen LiangShu-Yu LinShiao-Wei HuangYi-An ChiangHon-Tsen YuKay-Hooi KhooGeen-Dong ChangChu-Fang LoHan-Ching WangPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 6, p e1004196 (2014)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Mei-An Su
Yun-Tzu Huang
I-Tung Chen
Der-Yen Lee
Yun-Chieh Hsieh
Chun-Yuan Li
Tze Hann Ng
Suh-Yuen Liang
Shu-Yu Lin
Shiao-Wei Huang
Yi-An Chiang
Hon-Tsen Yu
Kay-Hooi Khoo
Geen-Dong Chang
Chu-Fang Lo
Han-Ching Wang
An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway.
description In this study, we used a systems biology approach to investigate changes in the proteome and metabolome of shrimp hemocytes infected by the invertebrate virus WSSV (white spot syndrome virus) at the viral genome replication stage (12 hpi) and the late stage (24 hpi). At 12 hpi, but not at 24 hpi, there was significant up-regulation of the markers of several metabolic pathways associated with the vertebrate Warburg effect (or aerobic glycolysis), including glycolysis, the pentose phosphate pathway, nucleotide biosynthesis, glutaminolysis and amino acid biosynthesis. We show that the PI3K-Akt-mTOR pathway was of central importance in triggering this WSSV-induced Warburg effect. Although dsRNA silencing of the mTORC1 activator Rheb had only a relatively minor impact on WSSV replication, in vivo chemical inhibition of Akt, mTORC1 and mTORC2 suppressed the WSSV-induced Warburg effect and reduced both WSSV gene expression and viral genome replication. When the Warburg effect was suppressed by pretreatment with the mTOR inhibitor Torin 1, even the subsequent up-regulation of the TCA cycle was insufficient to satisfy the virus's requirements for energy and macromolecular precursors. The WSSV-induced Warburg effect therefore appears to be essential for successful viral replication.
format article
author Mei-An Su
Yun-Tzu Huang
I-Tung Chen
Der-Yen Lee
Yun-Chieh Hsieh
Chun-Yuan Li
Tze Hann Ng
Suh-Yuen Liang
Shu-Yu Lin
Shiao-Wei Huang
Yi-An Chiang
Hon-Tsen Yu
Kay-Hooi Khoo
Geen-Dong Chang
Chu-Fang Lo
Han-Ching Wang
author_facet Mei-An Su
Yun-Tzu Huang
I-Tung Chen
Der-Yen Lee
Yun-Chieh Hsieh
Chun-Yuan Li
Tze Hann Ng
Suh-Yuen Liang
Shu-Yu Lin
Shiao-Wei Huang
Yi-An Chiang
Hon-Tsen Yu
Kay-Hooi Khoo
Geen-Dong Chang
Chu-Fang Lo
Han-Ching Wang
author_sort Mei-An Su
title An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway.
title_short An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway.
title_full An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway.
title_fullStr An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway.
title_full_unstemmed An invertebrate Warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the PI3K-Akt-mTOR pathway.
title_sort invertebrate warburg effect: a shrimp virus achieves successful replication by altering the host metabolome via the pi3k-akt-mtor pathway.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/bc700c6a000f4d76beffb3323cb67691
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