{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:57:19Z","timestamp":1786543039821,"version":"build-2736575974"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["5R21AI142862"],"award-info":[{"award-number":["5R21AI142862"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["EY5R01EY005093"],"award-info":[{"award-number":["EY5R01EY005093"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>This report evaluates how HSV enters the brain to cause herpes simplex encephalitis following infection at a peripheral site. We demonstrate that encephalitis regularly occurred when BALB\/c mice were infected with HSV and treated daily with 2-deoxy-d-glucose (2DG), which inhibits glucose use via the glycolysis pathway. The outcome of infection in the trigeminal ganglion (TG), the site to which the virus spreads, replicates, and establishes latency, showed marked differences in viral and cellular events between treated and untreated animals. In control-untreated mice, the replicating virus was present only during early time points, whereas in 2DG recipients, replicating virus remained for the 9-d observation period. This outcome correlated with significantly reduced numbers of innate inflammatory cells as well as T cells in 2DG-treated animals. Moreover, T cells in the TG of treated animals were less activated and contained a smaller fraction of expressed IFN-\u03b3 production compared with untreated controls. The breakdown of latency was accelerated when cultures of TG cells taken from mice with established HSV latency were cultured in the presence of 2DG. Taken together, the results of both in vivo and in vitro investigations demonstrate that the overall effects of 2DG therapy impaired the protective effects of one or more inflammatory cell types in the TG that normally function to control productive infection and prevent spread of virus to the brain.<\/jats:p>","DOI":"10.4049\/jimmunol.2100453","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T18:20:20Z","timestamp":1630520420000},"page":"1824-1835","source":"Crossref","is-referenced-by-count":12,"title":["Inhibiting Glucose Metabolism Results in Herpes Simplex Encephalitis"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0420-7714","authenticated-orcid":false,"given":"Engin","family":"Berber","sequence":"first","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee , Knoxville, TN"},{"name":"Department of Virology, Faculty of Veterinary Medicine, Erciyes University , Kayseri ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-255X","authenticated-orcid":false,"given":"Deepak","family":"Sumbria","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee , Knoxville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4759-8858","authenticated-orcid":false,"given":"Kim M","family":"Newkirk","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee , Knoxville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8829-0334","authenticated-orcid":false,"given":"Barry T","family":"Rouse","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee , Knoxville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"2025022610321594700_r1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1056\/NEJMra1708714","article-title":"Acute viral encephalitis","volume":"379","author":"Tyler","year":"2018","journal-title":"N. 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