title: To complete its replication cycle, a shrimp virus changes the population of long chain fatty acids during infection via the PI3K-Akt-mTOR-HIF1α pathway.
abstract: White spot syndrome virus (WSSV), the causative agent of white spot disease (WSD), is a serious and aggressive shrimp viral pathogen with a worldwide distribution. At the genome replication stage (12 hpi), WSSV induces a metabolic rerouting known as the invertebrate Warburg effect, which boosts the availability of energy and biosynthetic building blocks in the host cell. Here we show that unlike the lipogenesis that is seen in cancer cells that are undergoing the Warburg effect, at 12 hpi, all of the long chain fatty acids (LCFAs) were significantly decreased in the stomach cells of WSSV-infected shrimp. By means of this non-selective WSSV-induced lipolysis, the LCFAs were apparently diverted into β-oxidation and used to replenish the TCA cycle. Conversely, at 24 hpi, when the Warburg effect had ceased, most of the LCFAs were significantly up-regulated and the composition was also significantly altered. In crayfish these changes were in a direction that appeared to favor the formation of WSSV virion particles. We also found that, at 24 hpi, but not at 12 hpi, the PI3K-Akt-mTOR-HIF1α pathway induced the expression of fatty acid synthase (FAS), an enzyme which catalyzes the conversion of acetyl-CoA into LCFAs. WSSV virion formation was impaired in the presence of the FAS inhibitor C75, although viral gene and viral DNA levels were unaffected. WSSV therefore appears to use the PI3K-Akt-mTOR pathway to induce lipid biosynthesis at 24 hpi in order to support viral morphogenesis.
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yun-Chieh
authors.initials: YC
authors.lastname: Hsieh
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Li
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Core Facilities for Protein Structural Analysis, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Suh-Yuen
authors.initials: SY
authors.lastname: Liang
authors.affiliation: Academia Sinica Common Mass Spectrometry Facilities at Institute of Biological Chemistry, Taipei 115, Taiwan.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Sheng-Hsiung
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yi-Jan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Core Facilities for Protein Structural Analysis, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan. Electronic address: wanghc@mail.ncku.edu.tw.
authors.forename: Han-Ching
authors.initials: HC
authors.lastname: Wang
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005227:Fatty Acids / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008066:Lipolysis / Q000502:physiology; D033561:Penaeidae / Q000821:virology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D046848:White spot syndrome virus 1 / Q000378:metabolism*
chemical_list: D015107:4-Butyrolactone; D000105:Acetyl Coenzyme A; D064429:Fatty Acid Synthases; D005227:Fatty Acids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid
keywords: Lipid metabolism; Lipogenesis; Lipolysis; Long chain fatty acids; White spot syndrome virus