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Similarly, pretreatment of animals with IFN and experiments using mice defective in IFN signaling have indicated a role for IFN in controlling flavivirus disease in vivo. These data, along with findings that flavivirus-infected cells block IFN signaling, suggest that flavivirus infection can trigger an IFN response. To investigate IFN gene induction by the very first cells infected during in vivo infection with the flavivirus West Nile virus (WNV), we infected mice with high-titer preparations of WNV virus-like particles (VLPs), which initiate viral genome replication in cells but fail to spread. These studies demonstrated a brisk production of IFN in vivo, with peak levels of over 1,000 units\/ml detected in sera between 8 and 24 h after inoculation by either the intraperitoneal or footpad route. The IFN response was dependent on genome replication, and WNV genomes and WNV antigen-positive cells were readily detected in the popliteal lymph nodes (pLN) of VLP-inoculated mice. High levels of IFN mRNA transcripts and functional IFN were also produced in VLP-inoculated IFN regulatory factor 3 null (IRF3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice, indicating that IFN production was independent of the IRF3 pathways to IFN gene transcription, consistent with the IFN type produced (predominantly \u03b1).\n                  <\/jats:p>","DOI":"10.1128\/jvi.00316-07","type":"journal-article","created":{"date-parts":[[2007,6,14]],"date-time":"2007-06-14T00:04:37Z","timestamp":1181779477000},"page":"9100-9108","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":59,"title":["Early Production of Type I Interferon during West Nile Virus Infection: Role for Lymphoid Tissues in IRF3-Independent Interferon Production"],"prefix":"10.1128","volume":"81","author":[{"given":"Nigel","family":"Bourne","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555"},{"name":"Department of Pathology, UTMB, Galveston, Texas 77555"},{"name":"Department of Microbiology and Immunology, UTMB, Galveston, Texas 77555"},{"name":"Sealy Center for Vaccine Development, UTMB, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Scholle","sequence":"additional","affiliation":[{"name":"Department of Microbiology, North Carolina State University, Raleigh, North Carolina 27695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carlan","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pathology, UTMB, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannan L.","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Pathology, UTMB, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Dewsbury","sequence":"additional","affiliation":[{"name":"Department of Pathology, UTMB, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Judy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana B.","family":"De Aguiar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A.","family":"Leon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, North Carolina State University, Raleigh, North Carolina 27695"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Mark","family":"Estes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555"},{"name":"Department of Microbiology and Immunology, UTMB, Galveston, Texas 77555"},{"name":"Sealy Center for Vaccine Development, UTMB, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafik","family":"Fayzulin","sequence":"additional","affiliation":[{"name":"Department of Pathology, UTMB, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Pathology, UTMB, Galveston, Texas 77555"},{"name":"Department of Microbiology and Immunology, UTMB, Galveston, Texas 77555"},{"name":"Sealy Center for Vaccine Development, UTMB, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.20.12828-12839.2005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.7551"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(98)00063-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(02)00368-7"},{"key":"e_1_3_2_6_2","first-page":"24","volume":"19","year":"2006","unstructured":"Cao, W., and Y. 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