This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shrestha, B.
Right arrow Articles by Diamond, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shrestha, B.
Right arrow Articles by Diamond, M. S.

 Previous Article  |  Next Article 

Journal of Virology, June 2006, p. 5338-5348, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.00274-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Gamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection

Bimmi Shrestha,1 Tian Wang,2,{dagger} Melanie A. Samuel,3 Kevin Whitby,1 Joe Craft,2,4 Erol Fikrig,2 and Michael S. Diamond1,3,5*

Departments of Medicine,1 Molecular Microbiology,3 Pathology and Immunology, 660 S. Euclid Ave., Box 8051, Washington University School of Medicine, St. Louis, Missouri 63110,5 Sections of Rheumatology,2 Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 065204

Received 7 February 2006/ Accepted 8 March 2006

West Nile virus (WNV) causes a severe central nervous system (CNS) infection in humans, primarily in the elderly and immunocompromised. Prior studies have established an essential protective role of several innate immune response elements, including alpha/beta interferon (IFN-{alpha}/ß), immunoglobulin M, {gamma}{delta} T cells, and complement against WNV infection. In this study, we demonstrate that a lack of IFN-{gamma} production or signaling results in increased vulnerability to lethal WNV infection by a subcutaneous route in mice, with a rise in mortality from 30% (wild-type mice) to 90% (IFN-{gamma}–/– or IFN-{gamma}R–/– mice) and a decrease in the average survival time. This survival pattern in IFN-{gamma}–/– and IFN-{gamma}R–/– mice correlated with higher viremia and greater viral replication in lymphoid tissues. The increase in peripheral infection led to early CNS seeding since infectious WNV was detected several days earlier in the brains and spinal cords of IFN-{gamma}–/– or IFN-{gamma}R–/– mice. Bone marrow reconstitution experiments showed that {gamma}{delta} T cells require IFN-{gamma} to limit dissemination by WNV. Moreover, treatment of primary dendritic cells with IFN-{gamma} reduced WNV production by 130-fold. Collectively, our experiments suggest that the dominant protective role of IFN-{gamma} against WNV is antiviral in nature, occurs in peripheral lymphoid tissues, and prevents viral dissemination to the CNS.

* Corresponding author. Mailing address: Departments of Medicine, Molecular Microbiology, Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Ave., Box 8051, St. Louis, MO 63110. Phone: (314) 362-2842. Fax: (314) 362-9230. E-mail: diamond{at}borcim.wustl.edu.

{dagger} Present address: Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523.

Journal of Virology, June 2006, p. 5338-5348, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.00274-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Siddharthan, V., Wang, H., Motter, N. E., Hall, J. O., Skinner, R. D., Skirpstunas, R. T., Morrey, J. D. (2009). Persistent West Nile Virus Associated with a Neurological Sequela in Hamsters Identified by Motor Unit Number Estimation. J. Virol. 83: 4251-4261 [Abstract] [Full Text]  
  • Burdeinick-Kerr, R., Govindarajan, D., Griffin, D. E. (2009). Noncytolytic Clearance of Sindbis Virus Infection from Neurons by Gamma Interferon Is Dependent on Jak/Stat Signaling. J. Virol. 83: 3429-3435 [Abstract] [Full Text]  
  • Purtha, W. E., Chachu, K. A., Virgin, H. W. IV, Diamond, M. S. (2008). Early B-Cell Activation after West Nile Virus Infection Requires Alpha/Beta Interferon but Not Antigen Receptor Signaling. J. Virol. 82: 10964-10974 [Abstract] [Full Text]  
  • Daffis, S., Samuel, M. A., Suthar, M. S., Gale, M. Jr., Diamond, M. S. (2008). Toll-Like Receptor 3 Has a Protective Role against West Nile Virus Infection. J. Virol. 82: 10349-10358 [Abstract] [Full Text]  
  • Shrestha, B., Zhang, B., Purtha, W. E., Klein, R. S., Diamond, M. S. (2008). Tumor Necrosis Factor Alpha Protects against Lethal West Nile Virus Infection by Promoting Trafficking of Mononuclear Leukocytes into the Central Nervous System. J. Virol. 82: 8956-8964 [Abstract] [Full Text]  
  • Brehin, A.-C., Mouries, J., Frenkiel, M.-P., Dadaglio, G., Despres, P., Lafon, M., Couderc, T. (2008). Dynamics of Immune Cell Recruitment during West Nile Encephalitis and Identification of a New CD19+B220-BST-2+ Leukocyte Population. J. Immunol. 180: 6760-6767 [Abstract] [Full Text]  
  • Shrestha, B., Diamond, M. S. (2007). Fas Ligand Interactions Contribute to CD8+ T-Cell-Mediated Control of West Nile Virus Infection in the Central Nervous System. J. Virol. 81: 11749-11757 [Abstract] [Full Text]  
  • Sitati, E., McCandless, E. E., Klein, R. S., Diamond, M. S. (2007). CD40-CD40 Ligand Interactions Promote Trafficking of CD8+ T Cells into the Brain and Protection against West Nile Virus Encephalitis. J. Virol. 81: 9801-9811 [Abstract] [Full Text]  
  • Moraes, M. P., de los Santos, T., Koster, M., Turecek, T., Wang, H., Andreyev, V. G., Grubman, M. J. (2007). Enhanced Antiviral Activity against Foot-and-Mouth Disease Virus by a Combination of Type I and II Porcine Interferons. J. Virol. 81: 7124-7135 [Abstract] [Full Text]  
  • Burdeinick-Kerr, R., Wind, J., Griffin, D. E. (2007). Synergistic Roles of Antibody and Interferon in Noncytolytic Clearance of Sindbis Virus from Different Regions of the Central Nervous System. J. Virol. 81: 5628-5636 [Abstract] [Full Text]  
  • Samuel, M. A., Morrey, J. D., Diamond, M. S. (2007). Caspase 3-Dependent Cell Death of Neurons Contributes to the Pathogenesis of West Nile Virus Encephalitis. J. Virol. 81: 2614-2623 [Abstract] [Full Text]  
  • Wang, Y., Lobigs, M., Lee, E., Koskinen, A., Mullbacher, A. (2006). CD8+ T cell-mediated immune responses in West Nile virus (Sarafend strain) encephalitis are independent of gamma interferon. J. Gen. Virol. 87: 3599-3609 [Abstract] [Full Text]  
  • Samuel, M. A., Diamond, M. S. (2006). Pathogenesis of West Nile Virus Infection: a Balance between Virulence, Innate and Adaptive Immunity, and Viral Evasion. J. Virol. 80: 9349-9360 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»