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 Shresta, S.
Right arrow Articles by Harris, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shresta, S.
Right arrow Articles by Harris, E.

 Previous Article  |  Next Article 

Journal of Virology, March 2004, p. 2701-2710, Vol. 78, No. 6
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.6.2701-2710.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Interferon-Dependent Immunity Is Essential for Resistance to Primary Dengue Virus Infection in Mice, Whereas T- and B-Cell-Dependent Immunity Are Less Critical

Sujan Shresta,1 Jennifer L. Kyle,1,2 Heidi M. Snider,1 Manasa Basavapatna,1 P. Robert Beatty,3 and Eva Harris1*

Division of Infectious Diseases, School of Public Health,1 Graduate Group in Microbiology,2 Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 947203

Received 29 September 2003/ Accepted 1 December 2003

Dengue virus (DEN) causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, which are major public health problems worldwide. The immune factors that control DEN infection or contribute to severe disease are neither well understood nor easy to examine in humans. In this study, we used wild-type and congenic mice lacking various components of the immune system to study the immune mechanisms in the response to DEN infection. Our results demonstrate that alpha/beta interferon (IFN-{alpha}/ß) and IFN-{gamma} receptors have critical, nonoverlapping functions in resolving primary DEN infection. Furthermore, we show that IFN-{alpha}/ß receptor-mediated action limits initial DEN replication in extraneural sites and controls subsequent viral spread into the central nervous system (CNS). In contrast, IFN-{gamma} receptor-mediated responses seem to act at later stages of DEN disease by restricting viral replication in the periphery and eliminating virus from the CNS. Mice deficient in B, CD4+ T, or CD8+ T cells had no increased susceptibility to DEN; however, RAG mice (deficient in both B and T cells) were partially susceptible to DEN infection. In summary, (i) IFN-{alpha}/ß is critical for early immune responses to DEN infection, (ii) IFN-{gamma}-mediated immune responses are crucial for both early and late clearance of DEN infection in mice, and (iii) the IFN system plays a more important role than T- and B-cell-dependent immunity in resistance to primary DEN infection in mice.

* Corresponding author. Mailing address: Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 140 Warren Hall, Berkeley, CA 94720-7360. Phone: (510) 642-4845. Fax: (510) 642-6350. E-mail: eharris{at}socrates.berkeley.edu.

Journal of Virology, March 2004, p. 2701-2710, Vol. 78, No. 6
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.6.2701-2710.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gil, L., Lopez, C., Lazo, L., Valdes, I., Marcos, E., Alonso, R., Gambe, A., Martin, J., Romero, Y., Guzman, M. G., Guillen, G., Hermida, L. (2009). Recombinant nucleocapsid-like particles from dengue-2 virus induce protective CD4+ and CD8+ cells against viral encephalitis in mice. Int Immunol 21: 1175-1183 [Abstract] [Full Text]  
  • Souza, D. G., Fagundes, C. T., Sousa, L. P., Amaral, F. A., Souza, R. S., Souza, A. L., Kroon, E. G., Sachs, D., Cunha, F. Q., Bukin, E., Atrasheuskaya, A., Ignatyev, G., Teixeira, M. M. (2009). Essential role of platelet-activating factor receptor in the pathogenesis of Dengue virus infection. Proc. Natl. Acad. Sci. USA 106: 14138-14143 [Abstract] [Full Text]  
  • Perry, S. T., Prestwood, T. R., Lada, S. M., Benedict, C. A., Shresta, S. (2009). Cardif-Mediated Signaling Controls the Initial Innate Response to Dengue Virus In Vivo. J. Virol. 83: 8276-8281 [Abstract] [Full Text]  
  • Kamau, E., Takhampunya, R., Li, T., Kelly, E., Peachman, K. K., Lynch, J. A., Sun, P., Palmer, D. R. (2009). Dengue virus infection promotes translocation of high mobility group box 1 protein from the nucleus to the cytosol in dendritic cells, upregulates cytokine production and modulates virus replication. J. Gen. Virol. 90: 1827-1835 [Abstract] [Full Text]  
  • Balsitis, S. J., Coloma, J., Castro, G., Alava, A., Flores, D., McKerrow, J. H., Beatty, P. R., Harris, E. (2009). Tropism of Dengue Virus in Mice and Humans Defined by Viral Nonstructural Protein 3-Specific Immunostaining. Am J Trop Med Hyg 80: 416-424 [Abstract] [Full Text]  
  • Zurney, J., Kobayashi, T., Holm, G. H., Dermody, T. S., Sherry, B. (2009). Reovirus {micro}2 Protein Inhibits Interferon Signaling through a Novel Mechanism Involving Nuclear Accumulation of Interferon Regulatory Factor 9. J. Virol. 83: 2178-2187 [Abstract] [Full Text]  
  • Suzuki, R., Winkelmann, E. R., Mason, P. W. (2009). Construction and Characterization of a Single-Cycle Chimeric Flavivirus Vaccine Candidate That Protects Mice against Lethal Challenge with Dengue Virus Type 2. J. Virol. 83: 1870-1880 [Abstract] [Full Text]  
  • Brien, J. D., Uhrlaub, J. L., Nikolich-Zugich, J. (2008). West Nile Virus-Specific CD4 T Cells Exhibit Direct Antiviral Cytokine Secretion and Cytotoxicity and Are Sufficient for Antiviral Protection. J. Immunol. 181: 8568-8575 [Abstract] [Full Text]  
  • Umareddy, I., Tang, K. F., Vasudevan, S. G., Devi, S., Hibberd, M. L., Gu, F. (2008). Dengue virus regulates type I interferon signalling in a strain-dependent manner in human cell lines. J. Gen. Virol. 89: 3052-3062 [Abstract] [Full Text]  
  • Prestwood, T. R., Prigozhin, D. M., Sharar, K. L., Zellweger, R. M., Shresta, S. (2008). A Mouse-Passaged Dengue Virus Strain with Reduced Affinity for Heparan Sulfate Causes Severe Disease in Mice by Establishing Increased Systemic Viral Loads. J. Virol. 82: 8411-8421 [Abstract] [Full Text]  
  • Sariol, C. A., Munoz-Jordan, J. L., Abel, K., Rosado, L. C., Pantoja, P., Giavedoni, L., Rodriguez, I. V., White, L. J., Martinez, M., Arana, T., Kraiselburd, E. N. (2007). Transcriptional Activation of Interferon-Stimulated Genes but Not of Cytokine Genes after Primary Infection of Rhesus Macaques with Dengue Virus Type 1. CVI 14: 756-766 [Abstract] [Full Text]  
  • Srikiatkhachorn, A., Ajariyakhajorn, C., Endy, T. P., Kalayanarooj, S., Libraty, D. H., Green, S., Ennis, F. A., Rothman, A. L. (2007). Virus-Induced Decline in Soluble Vascular Endothelial Growth Receptor 2 Is Associated with Plasma Leakage in Dengue Hemorrhagic Fever. J. Virol. 81: 1592-1600 [Abstract] [Full Text]  
  • Chareonsirisuthigul, T., Kalayanarooj, S., Ubol, S. (2007). Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells. J. Gen. Virol. 88: 365-375 [Abstract] [Full Text]  
  • DEAUVIEAU, F., SANCHEZ, V., BALAS, C., KENNEL, A., DE MONTFORT, A., LANG, J., GUY, B. (2007). INNATE IMMUNE RESPONSES IN HUMAN DENDRITIC CELLS UPON INFECTION BY CHIMERIC YELLOW-FEVER DENGUE VACCINE SEROTYPES 1-4. Am J Trop Med Hyg 76: 144-154 [Abstract] [Full Text]  
  • Sitati, E. M., Diamond, M. S. (2006). CD4+ T-Cell Responses Are Required for Clearance of West Nile Virus from the Central Nervous System. J. Virol. 80: 12060-12069 [Abstract] [Full Text]  
  • Clyde, K., Kyle, J. L., Harris, E. (2006). Recent Advances in Deciphering Viral and Host Determinants of Dengue Virus Replication and Pathogenesis. J. Virol. 80: 11418-11431 [Full Text]  
  • Lee, E., Wright, P. J., Davidson, A., Lobigs, M. (2006). Virulence attenuation of Dengue virus due to augmented glycosaminoglycan-binding affinity and restriction in extraneural dissemination.. J. Gen. Virol. 87: 2791-2801 [Abstract] [Full Text]  
  • Shresta, S., Sharar, K. L., Prigozhin, D. M., Beatty, P. R., Harris, E. (2006). Murine Model for Dengue Virus-Induced Lethal Disease with Increased Vascular Permeability.. J. Virol. 80: 10208-10217 [Abstract] [Full Text]  
  • Hsieh, M.-F., Lai, S.-L., Chen, J.-P., Sung, J.-M., Lin, Y.-L., Wu-Hsieh, B. A., Gerard, C., Luster, A., Liao, F. (2006). Both CXCR3 and CXCL10/IFN-Inducible Protein 10 Are Required for Resistance to Primary Infection by Dengue Virus. J. Immunol. 177: 1855-1863 [Abstract] [Full Text]  
  • Samuel, M. A., Whitby, K., Keller, B. C., Marri, A., Barchet, W., Williams, B. R. G., Silverman, R. H., Gale, M. Jr., Diamond, M. S. (2006). PKR and RNase L Contribute to Protection against Lethal West Nile Virus Infection by Controlling Early Viral Spread in the Periphery and Replication in Neurons. J. Virol. 80: 7009-7019 [Abstract] [Full Text]  
  • Shrestha, B., Wang, T., Samuel, M. A., Whitby, K., Craft, J., Fikrig, E., Diamond, M. S. (2006). Gamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection.. J. Virol. 80: 5338-5348 [Abstract] [Full Text]  
  • Lopez, C. B., Yount, J. S., Hermesh, T., Moran, T. M. (2006). Sendai Virus Infection Induces Efficient Adaptive Immunity Independently of Type I Interferons. J. Virol. 80: 4538-4545 [Abstract] [Full Text]  
  • Liu, W. J., Wang, X. J., Clark, D. C., Lobigs, M., Hall, R. A., Khromykh, A. A. (2006). A Single Amino Acid Substitution in the West Nile Virus Nonstructural Protein NS2A Disables Its Ability To Inhibit Alpha/Beta Interferon Induction and Attenuates Virus Virulence in Mice. J. Virol. 80: 2396-2404 [Abstract] [Full Text]  
  • Calvert, A. E., Huang, C. Y.-H., Kinney, R. M., Roehrig, J. T. (2006). Non-structural proteins of dengue 2 virus offer limited protection to interferon-deficient mice after dengue 2 virus challenge. J. Gen. Virol. 87: 339-346 [Abstract] [Full Text]  
  • Samuel, M. A., Diamond, M. S. (2005). Alpha/Beta Interferon Protects against Lethal West Nile Virus Infection by Restricting Cellular Tropism and Enhancing Neuronal Survival. J. Virol. 79: 13350-13361 [Abstract] [Full Text]  
  • Shresta, S., Sharar, K. L., Prigozhin, D. M., Snider, H. M., Beatty, P. R., Harris, E. (2005). Critical Roles for Both STAT1-Dependent and STAT1-Independent Pathways in the Control of Primary Dengue Virus Infection in Mice. J. Immunol. 175: 3946-3954 [Abstract] [Full Text]  
  • Reuter, J. D., Wilson, J. H., Idoko, K. E, van den Pol, A. N. (2005). CD4+ T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain. J. Virol. 79: 9527-9539 [Abstract] [Full Text]  
  • Whitby, K., Pierson, T. C., Geiss, B., Lane, K., Engle, M., Zhou, Y., Doms, R. W., Diamond, M. S. (2005). Castanospermine, a Potent Inhibitor of Dengue Virus Infection In Vitro and In Vivo. J. Virol. 79: 8698-8706 [Abstract] [Full Text]  
  • Munoz-Jordan, J. L., Laurent-Rolle, M., Ashour, J., Martinez-Sobrido, L., Ashok, M., Lipkin, W. I., Garcia-Sastre, A. (2005). Inhibition of Alpha/Beta Interferon Signaling by the NS4B Protein of Flaviviruses. J. Virol. 79: 8004-8013 [Abstract] [Full Text]  
  • Ho, L.-J., Hung, L.-F., Weng, C.-Y., Wu, W.-L., Chou, P., Lin, Y.-L., Chang, D.-M., Tai, T.-Y., Lai, J.-H. (2005). Dengue Virus Type 2 Antagonizes IFN-{alpha} but Not IFN-{gamma} Antiviral Effect via Down-Regulating Tyk2-STAT Signaling in the Human Dendritic Cell. J. Immunol. 174: 8163-8172 [Abstract] [Full Text]  
  • Jones, M., Davidson, A., Hibbert, L., Gruenwald, P., Schlaak, J., Ball, S., Foster, G. R., Jacobs, M. (2005). Dengue Virus Inhibits Alpha Interferon Signaling by Reducing STAT2 Expression. J. Virol. 79: 5414-5420 [Abstract] [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»