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The IFN-\u03bbs were\u2014unlike alpha\/beta interferon (IFN-\u03b1\/\u03b2)\u2014induced directly by stimulation with IFN-\u03b1 or -\u03bb, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-\u03bbs have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN-\u03b1 potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-\u03b1 reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-\u03bb in vivo did not affect viral load after infection with EMCV or LCMV but did reduce the hepatic viral titer of HSV-2. In a model for a localized HSV-2 infection, we further found that IFN-\u03bb completely blocked virus replication in the vaginal mucosa and totally prevented development of disease, in contrast to IFN-\u03b1, which had a more modest antiviral activity. Finally, pretreatment with IFN-\u03bb enhanced the levels of IFN-\u03b3 in serum after HSV-2 infection. Thus, type III IFNs are expressed in response to most viruses and display potent antiviral activity in vivo against select viruses. The discrepancy between the observed antiviral activity in vitro and in vivo may suggest that IFN-\u03bb exerts a significant portion of its antiviral activity in vivo via stimulation of the immune system rather than through induction of the antiviral state.<\/jats:p>","DOI":"10.1128\/jvi.80.9.4501-4509.2006","type":"journal-article","created":{"date-parts":[[2006,4,12]],"date-time":"2006-04-12T19:38:32Z","timestamp":1144870712000},"page":"4501-4509","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":543,"title":["Lambda Interferon (IFN-\u03bb), a Type III IFN, Is Induced by Viruses and IFNs and Displays Potent Antiviral Activity against Select Virus Infections In Vivo"],"prefix":"10.1128","volume":"80","author":[{"given":"Nina","family":"Ank","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"West","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bartholdy","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Go\u0308teborg University, Go\u0308teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan R.","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren R.","family":"Paludan","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.16.8948-8956.2003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni736"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051395"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.80904-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(91)90018-U"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1990.tb01016.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)80066-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00154-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.189"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00237.2005"},{"key":"e_1_3_2_12_2","first-page":"371","volume":"129","year":"2005","unstructured":"Brand, S., F. 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