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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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) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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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. |
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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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