{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T09:13:41Z","timestamp":1776417221704,"version":"3.51.2"},"reference-count":40,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5844","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2007,9,14]]},"abstract":"<jats:p>Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3-independent pathways to prevent further dissemination of HSV-1 and to provide resistance to other pathogens in TLR3-deficient patients. Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3.<\/jats:p>","DOI":"10.1126\/science.1139522","type":"journal-article","created":{"date-parts":[[2007,9,13]],"date-time":"2007-09-13T17:09:55Z","timestamp":1189703395000},"page":"1522-1527","source":"Crossref","is-referenced-by-count":974,"title":["TLR3 Deficiency in Patients with Herpes Simplex Encephalitis"],"prefix":"10.1126","volume":"317","author":[{"given":"Shen-Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"Human Genetics of Infectious Diseases, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM), U550, Faculty Necker, Paris 75015, France."},{"name":"University Paris Rene\u0301 Descartes, Paris 75015, France."},{"name":"French-Chinese Laboratory of Genetics and Life Sciences, Rui Jin Hospital, Shanghai Jiao Tong 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We thank the children and their families for their participation in this study which was supported by the Schlumberger Foundation the BNP-Paribas Foundation the Groupement d'Int\u00e9r\u00eat Scientifique Maladies Rares the Action Concert\u00e9e Incitative de Microbiologie The March of Dimes and the Action Nationale pour la Recherche. P.R. is supported by a European Union FP6 grant. J.-L.C. is an international scholar of the Howard Hughes Medical Institute."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1139522","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T04:01:12Z","timestamp":1704859272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1139522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,14]]},"references-count":40,"journal-issue":{"issue":"5844","published-print":{"date-parts":[[2007,9,14]]}},"alternative-id":["10.1126\/science.1139522"],"URL":"https:\/\/doi.org\/10.1126\/science.1139522","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1091813.580536","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1091813.545120","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1091813.545194","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,9,14]]}}}