{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:46:38Z","timestamp":1789519598411,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["BMRP819, BMRP564, CMRPD1H0201, CMRPD1H0202, CMRPD1J0341, CMRPD1H0511, CMRPD1J0261"],"award-info":[{"award-number":["BMRP819, BMRP564, CMRPD1H0201, CMRPD1H0202, CMRPD1J0341, CMRPD1H0511, CMRPD1J0261"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education in Taiwan","award":["EMRPD1G0251, EMRPD1H0401, EMRPD1I0501, EMRPD1I0461"],"award-info":[{"award-number":["EMRPD1G0251, EMRPD1H0401, EMRPD1I0501, EMRPD1I0461"]}]},{"name":"Ministry of Science and Technology in Taiwan","award":["MOST 107-2320-B-182-011-MY3,  MOST 108-2320-B-182-006, MOST 108\u20103017\u2010F\u2010182\u2010001"],"award-info":[{"award-number":["MOST 107-2320-B-182-011-MY3,  MOST 108-2320-B-182-006, MOST 108\u20103017\u2010F\u2010182\u2010001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Enterovirus 71 (EV71) infection is an endemic disease in Southeast Asia and China. We have previously shown that EV71 virus causes functional changes in mitochondria. It is speculative whether EV71 virus alters the host cell metabolism to its own benefit. Using a metabolomics approach, we demonstrate that EV71-infected Vero cells had significant changes in metabolism. Glutathione and its related metabolites, and several amino acids, such as glutamate and aspartate, changed significantly with the infectious dose of virus. Other pathways, including glycolysis and tricarboxylic acid cycle, were also altered. A change in glutamine\/glutamate metabolism is critical to the viral infection. The presence of glutamine in culture medium was associated with an increase in viral replication. Dimethyl \u03b1-ketoglutarate treatment partially mimicked the effect of glutamine supplementation. In addition, the immunoblot analysis revealed that the expression of glutamate dehydrogenase (GDH) and trifunctional carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) increased during infection. Knockdown of expression of glutaminase (GLS), GDH and CAD drastically reduced the cytopathic effect (CPE) and viral replication. Furthermore, we found that CAD bound VP1 to promote the de novo pyrimidine synthesis. Our findings suggest that virus may induce metabolic reprogramming of host cells to promote its replication through interactions between viral and host cell proteins.<\/jats:p>","DOI":"10.3390\/cells9020473","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T04:21:26Z","timestamp":1582604486000},"page":"473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Metabolic Reprogramming of Host Cells in Response to Enteroviral Infection"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2006-133X","authenticated-orcid":false,"given":"Mei-Ling","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Healthy Aging Research Center, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Yi","family":"Chien","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hsueh","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4595-5754","authenticated-orcid":false,"given":"Guan-Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1890-6786","authenticated-orcid":false,"given":"Jui-Fen","family":"Lin","sequence":"additional","affiliation":[{"name":"Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5990-6622","authenticated-orcid":false,"given":"Hung-Yao","family":"Ho","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan"},{"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ref_1","unstructured":"Fields, B., Knipe, D.M., and Howley, P.M. 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