{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:49:46Z","timestamp":1791132586242,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2006,11,1]],"date-time":"2006-11-01T00:00:00Z","timestamp":1162339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>TLR3 was the first member of the TLR family of pattern recognition receptors found to detect a conserved viral molecular pattern, dsRNA, yet supporting evidence for a major role in host defense against viral pathogens is limited. Punta Toro virus (PTV) has been shown to produce severe infection in mice, modeling disease caused by the related highly pathogenic Rift Valley fever phlebovirus in humans and domesticated ungulates. Using TLR3-deficient mice, we investigated the involvement of TLR3 in host defense against PTV infection. Compared with wild-type, TLR3\u2212\/\u2212 mice demonstrate increased resistance to lethal infection and have reduced liver disease associated with hepatotropic PTV infection. Infectious challenge produced comparable peak liver and serum viral loads; however, TLR3\u2212\/\u2212 mice were able to clear systemic virus at a slightly faster rate. Cytokine profiling suggests that TLR3 plays an important role in PTV pathogenesis through the overproduction of inflammatory mediators, which may be central to the observed differences in survival and disease severity. Compared with TLR3-deficient mice, IL-6, MCP-1, IFN-\u03b3, and RANTES were all present at higher levels in wild-type animals. Most dramatic was the exaggerated levels of IL-6 found systemically and in liver tissue of infected wild-type mice; however, IL-6-deficient animals were found to be more susceptible to lethal PTV infection. Taken together, we conclude that the TLR3-mediated response to PTV infection is detrimental to disease outcome and propose that IL-6, although critical to establishing antiviral defense, contributes to pathogenesis when released in excess, necessitating its controlled production as is seen with TLR3\u2212\/\u2212 mice.<\/jats:p>","DOI":"10.4049\/jimmunol.177.9.6301","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:02:17Z","timestamp":1397862137000},"page":"6301-6307","source":"Crossref","is-referenced-by-count":103,"title":["TLR3 Deletion Limits Mortality and Disease Severity due to Phlebovirus Infection"],"prefix":"10.1093","volume":"177","author":[{"given":"Brian B","family":"Gowen","sequence":"first","affiliation":[{"name":"Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University , Logan, UT 84322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin D","family":"Hoopes","sequence":"additional","affiliation":[{"name":"Department of Biology, Utah State University , Logan, UT 84322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hui","family":"Wong","sequence":"additional","affiliation":[{"name":"Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University , Logan, UT 84322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kie-Hoon","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University , Logan, UT 84322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C","family":"Isakson","sequence":"additional","affiliation":[{"name":"Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University , Logan, UT 84322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Alexopoulou","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-Institut National de la Sante et de la Recherche Medicale , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Flavell","sequence":"additional","affiliation":[{"name":"Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Sidwell","sequence":"additional","affiliation":[{"name":"Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University , Logan, UT 84322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,11,1]]},"reference":[{"key":"2025032704244791800_R1","first-page":"499","volume-title":"Nat. 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