{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T04:30:01Z","timestamp":1769229001354,"version":"3.49.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T00:00:00Z","timestamp":1562112000000},"content-version":"am","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Herpes zoster ophthalmicus occurs primarily in elderly or immunocompromised individuals after reactivation of varicella zoster virus (VZV). Recurrences of zoster ophthalmicus are uncommon because the reactivation efficiently boosts anti-VZV immunity. A 28-year-old female presented to our clinic with a history of multiple recurrences of zoster ophthalmicus.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Whole-exome sequencing (WES), analyses of VZV T-cell immunity, and pathogen recognition receptor function in primary antigen-presenting cells (APCs) and fibroblasts were performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Normal VZV-specific T-cell immunity and antibody response were detected. Whole-exome sequencing identified a heterozygous nonsynonymous variant (c.2324C &gt; T) in the Toll-like receptor 3 (TLR3) gene resulting in formation of a premature stop-codon. This alteration could potentially undermine TLR3 signaling in a dominant-negative fashion. Therefore, we investigated TLR3 signaling responses in APCs and fibroblasts from the patient. The APCs responded efficiently to stimulation with TLR3 ligands, whereas the responses from the fibroblasts were compromised.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We report a novel TLR3 variant associated with recurrent zoster ophthalmicus. Toll-like receptor 3 responses that were unaffected in APCs but diminished in fibroblasts are in line with previous reports linking TLR3 deficiency with herpes simplex virus encephalitis. Mechanisms involving compromised viral sensing in infected cells may thus be central to the described immunodeficiency.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiz229","type":"journal-article","created":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T19:10:33Z","timestamp":1556824233000},"source":"Crossref","is-referenced-by-count":8,"title":["Recurrent Herpes Zoster Ophthalmicus in a Patient With a Novel Toll-Like Receptor 3 Variant Linked to Compromised Activation Capacity in Fibroblasts"],"prefix":"10.1093","author":[{"given":"Frank","family":"Liang","sequence":"first","affiliation":[{"name":"Division of Immunology and Allergy, Department of Medicine Solna"},{"name":"Center for Molecular Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hedvig","family":"Glans","sequence":"additional","affiliation":[{"name":"Division of Dermatology and Venerology, Department of Medicine Solna, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara Lind","family":"Enoksson","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Clinical Immunology, Karolinska University Hospital, Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonios G A","family":"Kolios","sequence":"additional","affiliation":[{"name":"Department of Immunology, University Hospital Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Lor\u00e9","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Department of Medicine Solna"},{"name":"Center for Molecular Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5091-8133","authenticated-orcid":false,"given":"Jakob","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Immunology, University Hospital Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"2019070305524621100_CIT0001","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrmicro3215","article-title":"Molecular mechanisms of varicella zoster virus pathogenesis","volume":"12","author":"Zerboni","year":"2014","journal-title":"Nat Rev Microbiol"},{"key":"2019070305524621100_CIT0002","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nri2937","article-title":"Recognition of herpesviruses by the innate immune system","volume":"11","author":"Paludan","year":"2011","journal-title":"Nat Rev 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