{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:25:08Z","timestamp":1781886308537,"version":"3.54.5"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T00:00:00Z","timestamp":1595808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/RLF\/Re-entry\/60\/2013"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/60\/2013"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["EMR\/2016\/007608"],"award-info":[{"award-number":["EMR\/2016\/007608"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Epstein\u2013Barr virus or human herpesvirus 4 (EBV\/HHV-4) is a ubiquitous human virus associated with a wide range of malignant neoplasms. The interaction between EBV latent proteins and host cellular molecules often leads to oncogenic transformation, promoting the development of EBV-associated cancers. The present study identifies a functional role of GLS1 isoforms KGA and GAC in regulating mitochondrial energy metabolism to promote EBV-infected cell proliferation. Our data demonstrate increased expression of GLS1 isoforms KGA and GAC with mitochondrial localization in latently EBV-infected cells and de novo EBV-infected PBMCs. c-Myc upregulates KGA and GAC protein levels, which in turn elevate the levels of intracellular glutamate. Further analysis demonstrated upregulated expression of mitochondrial GLUD1 and GLUD2, with a subsequent increase in alpha-ketoglutarate levels that may mark the activation of glutaminolysis. Cell proliferation and viability of latently EBV-infected cells were notably inhibited by KGA\/GAC, as well as GLUD1 inhibitors. Taken together, our results suggest that c-Myc-dependent regulation of KGA and GAC enhances mitochondrial functions to support the rapid proliferation of the EBV-infected cells, and these metabolic processes could be therapeutically exploited by targeting KGA\/GAC and GLUD1 to prevent EBV-associated cancers.<\/jats:p>","DOI":"10.3390\/v12080811","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T10:16:49Z","timestamp":1595931409000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Upregulation of GLS1 Isoforms KGA and GAC Facilitates Mitochondrial Metabolism and Cell Proliferation in Epstein\u2013Barr Virus Infected Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Gayathri","family":"Krishna","sequence":"first","affiliation":[{"name":"Virology Laboratory, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682022, Kerala, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Soman Pillai","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682022, Kerala, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohanan","family":"Valiya Veettil","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682022, Kerala, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"ref_1","first-page":"581","article-title":"Epstein-Barr virus and nasopharyngeal carcinoma","volume":"33","author":"Young","year":"2014","journal-title":"Chin. 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