{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:05:58Z","timestamp":1789470358825,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010387","name":"Universidad de Sonora","doi-asserted-by":"publisher","award":["USO513007035"],"award-info":[{"award-number":["USO513007035"]}],"id":[{"id":"10.13039\/501100010387","id-type":"DOI","asserted-by":"publisher"}]},{"award":["USO513007035"],"award-info":[{"award-number":["USO513007035"]}],"id":[{"id":"https:\/\/ror.org\/00c32gy34","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hypoxia-inducible factor-1 (HIF-1) induces the Warburg effect in the Litopenaeus vannamei shrimp infected with white spot syndrome virus (WSSV) to satisfy the energetic and biosynthetic demands required for viral replication. Glycerol-3-phosphate dehydrogenase (GPDH) is a key enzyme linking carbohydrate metabolism, lipid biosynthesis, and cellular redox balance; however, its role during WSSV infection remains poorly understood. In this study, the complete coding sequences of the cytoplasmic (LvGPDHc) and mitochondrial (LvGPDHm) GPDH isoforms were characterized from the hepatopancreas of L. vannamei, and their regulation by HIF-1\u03b1 during WSSV infection was investigated. Sequence and phylogenetic analyses revealed that both proteins are highly conserved among crustaceans and contain the characteristic domains required for catalytic activity. WSSV infection decreases the mRNA expression of both GPDH isoforms and increases the cytoplasmic GPDH activity. In contrast, HIF-1\u03b1 silencing increases the mRNA expression of both GPDH isoforms and increases the mitochondrial GPDH activity. The concentrations of glycerol-3-phosphate and citrate increase with WSSV infection and return to basal levels upon HIF-1\u03b1 silencing. Results suggest that WSSV infection in white shrimp is associated with increased lipid biosynthesis via cytoplasmic GPDH, which contributes to viral replication, whereas mitochondrial GPDH may help maintain cellular redox status. Furthermore, these results demonstrate that the expression of GPDH isoforms is regulated by HIF-1, contributing to metabolic reprogramming in shrimp during WSSV infection.<\/jats:p>","DOI":"10.3390\/v18091020","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:32:01Z","timestamp":1789468321000},"page":"1020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of Glycerol-3-Phosphate Dehydrogenase by Hypoxia-Inducible Factor-1 in WSSV-Infected White Shrimp Litopenaeus vannamei"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-3503","authenticated-orcid":false,"given":"Jes\u00fas Alfredo","family":"Rosas-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmico-Biol\u00f3gicas y Agropecuarias, Facultad Interdisciplinaria de Ciencias Biol\u00f3gicas y de Salud, Universidad de Sonora, Navojoa 85880, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Cesar","family":"Mu\u00f1oz-Bacasehua","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmico-Biol\u00f3gicas y Agropecuarias, Facultad Interdisciplinaria de Ciencias Biol\u00f3gicas y de Salud, Universidad de Sonora, Navojoa 85880, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guadalupe","family":"Gonz\u00e1lez-Ochoa","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmico-Biol\u00f3gicas y Agropecuarias, Facultad Interdisciplinaria de Ciencias Biol\u00f3gicas y de Salud, Universidad de Sonora, Navojoa 85880, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8738-8199","authenticated-orcid":false,"given":"Enrico Alejandro","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Departamento de Zoolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Colonia Santo Tom\u00e1s, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4710-7369","authenticated-orcid":false,"given":"Misael Daniel","family":"Mancilla-Morales","sequence":"additional","affiliation":[{"name":"Estaci\u00f3n Cient\u00edfica La Malinche, Centro Tlaxcala de Biolog\u00eda de la Conducta, Universidad Aut\u00f3noma de Tlaxcala, Tlaxcala 90000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Luis Alberto","family":"Zamora-Alvarez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmico-Biol\u00f3gicas y Agropecuarias, Facultad Interdisciplinaria de Ciencias Biol\u00f3gicas y de Salud, Universidad de Sonora, Navojoa 85880, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jos\u00e9 Guadalupe","family":"So\u00f1anez-Organis","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmico-Biol\u00f3gicas y Agropecuarias, Facultad Interdisciplinaria de Ciencias Biol\u00f3gicas y de Salud, Universidad de Sonora, Navojoa 85880, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6031","DOI":"10.1016\/S0021-9258(18)63577-X","article-title":"Purification and Properties of Two Types of Diphosphopyridine Nucleotide-Linked Glycerol 3-Phosphate Dehydrogenases from Chicken Breast Muscle and Chicken Liver","volume":"244","author":"White","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1042\/bj1460223","article-title":"Role of Glycerol 3 Phosphate Dehydrogenase in Glyceride Metabolism. Effect of Diet on Enzyme Activities in Chicken Liver","volume":"146","author":"Harding","year":"1975","journal-title":"Biochem. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1107\/S1744309112037736","article-title":"Structure of Glycerol-3-Phosphate Dehydrogenase (GPD1) from Saccharomyces Cerevisiae at 2.45 \u00c5 Resolution","volume":"68","author":"Alarcon","year":"2012","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8042","DOI":"10.1016\/S0021-9258(19)57509-3","article-title":"Purification and Characterization of Glycerol-3-Phosphate Dehydrogenase (Flavin-Linked) from Rat Liver Mitochondria","volume":"261","author":"Garrib","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/BF01659162","article-title":"Separate Physiological Roles for Two Isozymes of Pyridine Nucleotide-Linked Glycerol-3-Phosphate Dehydrogenase in Chicken","volume":"1","author":"White","year":"1972","journal-title":"J. Mol. Evol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12919","DOI":"10.1128\/JVI.05385-11","article-title":"White Spot Syndrome Virus Induces Metabolic Changes Resembling the Warburg Effect in Shrimp Hemocytes in the Early Stage of Infection","volume":"85","author":"Chen","year":"2011","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.fsi.2018.01.011","article-title":"Regulation of Lactate Dehydrogenase in Response to WSSV Infection in the Shrimp Litopenaeus vannamei","volume":"74","author":"Ortiz","year":"2018","journal-title":"Fish Shellfish Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.fsi.2019.05.040","article-title":"Hypoxia Inducible Factor \u22121 Regulates WSSV-Induced Glycolytic Genes in the White Shrimp Litopenaeus vannamei","volume":"92","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Su, M.A., Huang, Y.T., Chen, I.T., Lee, D.Y., Hsieh, Y.C., Li, C.Y., Ng, T.H., Liang, S.Y., Lin, S.Y., and Huang, S.W. (2014). An Invertebrate Warburg Effect: A Shrimp Virus Achieves Successful Replication by Altering the Host Metabolome via the PI3K-Akt-MTOR Pathway. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004196"},{"key":"ref_10","first-page":"19","article-title":"Silencing of HIF-1 in WSSV-Infected White Shrimp: Effect on Viral Load and Antioxidant Enzymes","volume":"213","author":"Ortiz","year":"2018","journal-title":"Comp. Biochem. Physiol. Part\u2014C Toxicol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/S0959-437X(98)80016-6","article-title":"Hypoxia-Inducible Factor 1: Master Regulator of O2 Homeostasis","volume":"8","author":"Semenza","year":"1998","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.dci.2017.01.018","article-title":"Triosephosphate Isomerase (TPI) Facilitates the Replication of WSSV in Exopalaemon carinicauda","volume":"71","author":"Li","year":"2017","journal-title":"Dev. Comp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1046\/j.1365-2761.2002.00367.x","article-title":"Quantitative Real Time PCR for the Measurement of White Spot Syndrome Virus in Shrimp","volume":"25","author":"Durand","year":"2002","journal-title":"J. Fish Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1093\/molbev\/msab120","article-title":"MEGA11: Molecular Evolutionary Genetics Analysis Version 11","volume":"38","author":"Tamura","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1093\/molbev\/msn067","article-title":"An Improved General Amino Acid Replacement Matrix","volume":"25","author":"Le","year":"2008","journal-title":"Mol. Biol. Evol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pecinov\u00e1, A., Al\u00e1n, L., Br\u00e1zdov\u00e1, A., Vrback\u00fd, M., Pecina, P., Drahota, Z., Hou\u0161t\u011bk, J., and Mr\u00e1\u010dek, T. (2020). Role of Mitochondrial Glycerol-3-Phosphate Dehydrogenase in Metabolic Adaptations of Prostate Cancer. Cells, 9.","DOI":"10.3390\/cells9081764"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.bbabio.2012.11.014","article-title":"The Function and the Role of the Mitochondrial Glycerol-3-Phosphate Dehydrogenase in Mammalian Tissues","volume":"1827","author":"Drahota","year":"2013","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.tim.2011.03.007","article-title":"Multifaceted Roles for Lipids in Viral Infection","volume":"19","author":"Heaton","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Thaker, S.K., Ch\u2019ng, J., and Christofk, H.R. (2019). Viral Hijacking of Cellular Metabolism. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0678-9"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.cmet.2014.03.009","article-title":"Adenovirus E4ORF1-Induced MYC Activation Promotes Host Cell Anabolic Glucose Metabolism and Virus Replication","volume":"19","author":"Thai","year":"2014","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2016.03.014","article-title":"On the Dependency of Cellular Protein Levels on MRNA Abundance","volume":"165","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the Regulation of Protein Abundance from Proteomic and Transcriptomic Analyses","volume":"13","author":"Vogel","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.tibs.2018.12.007","article-title":"Interconnection between Metabolism and Cell Cycle in Cancer","volume":"44","author":"Icard","year":"2019","journal-title":"Trends Biochem. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pant, A., Dsouza, L., Cao, S., Peng, C., and Yang, Z. (2021). Viral Growth Factor- and STAT3 Signaling-dependent Elevation of the TCA Cycle Intermediate Levels during Vaccinia Virus Infection. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009303"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/cei.12591","article-title":"Citrate Modulates Lipopolysaccharide-Induced Monocyte Inflammatory Responses","volume":"180","author":"Ashbrook","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Garc\u00eda, F.J., P\u00e9rez-Hern\u00e1ndez, C.A., Rodr\u00edguez-Murillo, M., and Moreno-Altamirano, M.M.B. (2021). The Role of Tricarboxylic Acid Cycle Metabolites in Viral Infections. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.725043"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1139\/cjm-2014-0485","article-title":"Impact of Glycerol-3-Phosphate Dehydrogenase on Virulence Factor Production by Pseudomonas Aeruginosa","volume":"60","author":"Daniels","year":"2014","journal-title":"Can. J. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1099\/mic.0.000646","article-title":"Transcriptome Analysis of a Pseudomonas Aeruginosa Sn-Glycerol-3-Phosphate Dehydrogenase Mutant Reveals a Disruption in Bioenergetics","volume":"164","author":"Shuman","year":"2018","journal-title":"Microbiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1038\/s41590-019-0453-7","article-title":"Glycerol Phosphate Shuttle Enzyme GPD2 Regulates Macrophage Inflammatory Responses","volume":"20","author":"Langston","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1139\/cjm-2016-0119","article-title":"Glycerol Metabolism Promotes Biofilm Formation by Pseudomonas Aeruginosa","volume":"62","author":"Scoffield","year":"2016","journal-title":"Can. J. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e0262422","DOI":"10.1128\/mbio.02624-22","article-title":"Metabolic Mechanism and Physiological Role of Glycerol 3-Phosphate in Pseudomonas Aeruginosa PAO1","volume":"13","author":"Liu","year":"2022","journal-title":"mBio"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Shi, Y., Wang, H., Yan, Y., Cao, H., Liu, X., Lin, F., and Lu, J. (2018). Glycerol-3-Phosphate Shuttle Is Involved in Development and Virulence in the Rice Blast Fungus Pyricularia oryzae. Front. Plant Sci., 9.","DOI":"10.3389\/fpls.2018.00687"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/9\/1020\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:36:28Z","timestamp":1789468588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/9\/1020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":32,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["v18091020"],"URL":"https:\/\/doi.org\/10.3390\/v18091020","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}