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Journal of Virology, September 2007, p. 9100-9108, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00316-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Early Production of Type I Interferon during West Nile Virus Infection: Role for Lymphoid Tissues in IRF3-Independent Interferon Production{triangledown}

Nigel Bourne,1,2,3,4 Frank Scholle,5 Maria Carlan Silva,2 Shannan L. Rossi,2 Nathan Dewsbury,2 Barbara Judy,1 Juliana B. De Aguiar,1 Megan A. Leon,5 D. Mark Estes,1,3,4 Rafik Fayzulin,2 and Peter W. Mason2,3,4*

Department of Pediatrics, University of Texas Medical Branch (UTMB), Galveston, Texas 77555,1 Department of Pathology, UTMB, Galveston, Texas 77555,2 Department of Microbiology and Immunology, UTMB, Galveston, Texas 77555,3 Sealy Center for Vaccine Development, UTMB, Galveston, Texas 77555,4 Department of Microbiology, North Carolina State University, Raleigh, North Carolina 276955

Received 12 February 2007/ Accepted 4 June 2007

Infection of cells with flaviviruses in vitro is reduced by pretreatment with small amounts of type I interferon (IFN-{alpha}/ß). 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–/–) mice, indicating that IFN production was independent of the IRF3 pathways to IFN gene transcription, consistent with the IFN type produced (predominantly {alpha}).

* Corresponding author. Mailing address: Department of Pathology, 3.206B Mary Moody Northen Pavilion, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0436. Phone: (409) 747-8143. Fax: (409) 747-8150. E-mail: pwmason{at}utmb.edu

{triangledown} Published ahead of print on 13 June 2007.

Journal of Virology, September 2007, p. 9100-9108, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00316-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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