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 Liu, W. J.
Right arrow Articles by Khromykh, A. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, W. J.
Right arrow Articles by Khromykh, A. A.

 Previous Article  |  Next Article 

Journal of Virology, February 2005, p. 1934-1942, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1934-1942.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inhibition of Interferon Signaling by the New York 99 Strain and Kunjin Subtype of West Nile Virus Involves Blockage of STAT1 and STAT2 Activation by Nonstructural Proteins{dagger}

Wen Jun Liu,1,2 Xiang Ju Wang,1,2 Vladislav V. Mokhonov,1,2 Pei-Yong Shi,3 Richard Randall,4 and Alexander A. Khromykh1,2*

Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital,1 Clinical Medical Virology Centre, University of Queensland, Brisbane, Queensland, Australia,2 Wadsworth Centre, New York State Department of Health, Albany, New York,3 University of St. Andrews, St. Andrews, Scotland4

Received 7 May 2004/ Accepted 20 October 2004

The interferon (IFN) response is the first line of defense against viral infections, and the majority of viruses have developed different strategies to counteract IFN responses in order to ensure their survival in an infected host. In this study, the abilities to inhibit IFN signaling of two closely related West Nile viruses, the New York 99 strain (NY99) and Kunjin virus (KUN), strain MRM61C, were analyzed using reporter plasmid assays, as well as immunofluorescence and Western blot analyses. We have demonstrated that infections with both NY99 and KUN, as well as transient or stable transfections with their replicon RNAs, inhibited the signaling of both alpha/beta IFN (IFN-{alpha}/ß) and gamma IFN (IFN-{gamma}) by blocking the phosphorylation of STAT1 and its translocation to the nucleus. In addition, the phosphorylation of STAT2 and its translocation to the nucleus were also blocked by KUN, NY99, and their replicons in response to treatment with IFN-{alpha}. IFN-{alpha} signaling and STAT2 translocation to the nucleus was inhibited when the KUN nonstructural proteins NS2A, NS2B, NS3, NS4A, and NS4B, but not NS1 and NS5, were expressed individually from the pcDNA3 vector. The results clearly demonstrate that both NY99 and KUN inhibit IFN signaling by preventing STAT1 and STAT2 phosphorylation and identify nonstructural proteins responsible for this inhibition.

* Corresponding author. Mailing address: Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, Queensland 4029, Australia. Phone: 617 36361568. Fax: 617 36361401. E-mail: a.khromykh{at}uq.edu.au.

{dagger} This is publication 208 from the Clinical Medical Virology Centre and the Sir Albert Sakzewski Virus Research Centre.

Journal of Virology, February 2005, p. 1934-1942, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1934-1942.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ashour, J., Laurent-Rolle, M., Shi, P.-Y., Garcia-Sastre, A. (2009). NS5 of Dengue Virus Mediates STAT2 Binding and Degradation. J. Virol. 83: 5408-5418 [Abstract] [Full Text]  
  • Holloway, G., Truong, T. T., Coulson, B. S. (2009). Rotavirus Antagonizes Cellular Antiviral Responses by Inhibiting the Nuclear Accumulation of STAT1, STAT2, and NF-{kappa}B. J. Virol. 83: 4942-4951 [Abstract] [Full Text]  
  • Daffis, S., Samuel, M. A., Suthar, M. S., Keller, B. C., Gale, M. Jr., Diamond, M. S. (2008). Interferon Regulatory Factor IRF-7 Induces the Antiviral Alpha Interferon Response and Protects against Lethal West Nile Virus Infection. J. Virol. 82: 8465-8475 [Abstract] [Full Text]  
  • Wilson, J. R., de Sessions, P. F., Leon, M. A., Scholle, F. (2008). West Nile Virus Nonstructural Protein 1 Inhibits TLR3 Signal Transduction. J. Virol. 82: 8262-8271 [Abstract] [Full Text]  
  • Kong, K.-F., Delroux, K., Wang, X., Qian, F., Arjona, A., Malawista, S. E., Fikrig, E., Montgomery, R. R. (2008). Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly. J. Virol. 82: 7613-7623 [Abstract] [Full Text]  
  • Suzuki, R., Fayzulin, R., Frolov, I., Mason, P. W. (2008). Identification of Mutated Cyclization Sequences That Permit Efficient Replication of West Nile Virus Genomes: Use in Safer Propagation of a Novel Vaccine Candidate. J. Virol. 82: 6942-6951 [Abstract] [Full Text]  
  • Leung, J. Y., Pijlman, G. P., Kondratieva, N., Hyde, J., Mackenzie, J. M., Khromykh, A. A. (2008). Role of Nonstructural Protein NS2A in Flavivirus Assembly. J. Virol. 82: 4731-4741 [Abstract] [Full Text]  
  • Fredericksen, B. L., Keller, B. C., Fornek, J., Katze, M. G., Gale, M. Jr. (2008). Establishment and Maintenance of the Innate Antiviral Response to West Nile Virus Involves both RIG-I and MDA5 Signaling through IPS-1. J. Virol. 82: 609-616 [Abstract] [Full Text]  
  • Randall, R. E., Goodbourn, S. (2008). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89: 1-47 [Abstract] [Full Text]  
  • Silva, M. C., Guerrero-Plata, A., Gilfoy, F. D., Garofalo, R. P., Mason, P. W. (2007). Differential Activation of Human Monocyte-Derived and Plasmacytoid Dendritic Cells by West Nile Virus Generated in Different Host Cells. J. Virol. 81: 13640-13648 [Abstract] [Full Text]  
  • Evans, J. D., Seeger, C. (2007). Differential Effects of Mutations in NS4B on West Nile Virus Replication and Inhibition of Interferon Signaling. J. Virol. 81: 11809-11816 [Abstract] [Full Text]  
  • Noueiry, A. O., Olivo, P. D., Slomczynska, U., Zhou, Y., Buscher, B., Geiss, B., Engle, M., Roth, R. M., Chung, K. M., Samuel, M., Diamond, M. S. (2007). Identification of Novel Small-Molecule Inhibitors of West Nile Virus Infection. J. Virol. 81: 11992-12004 [Abstract] [Full Text]  
  • Scherbik, S. V., Stockman, B. M., Brinton, M. A. (2007). Differential Expression of Interferon (IFN) Regulatory Factors and IFN-Stimulated Genes at Early Times after West Nile Virus Infection of Mouse Embryo Fibroblasts. J. Virol. 81: 12005-12018 [Abstract] [Full Text]  
  • Gilfoy, F. D., Mason, P. W. (2007). West Nile Virus-Induced Interferon Production Is Mediated by the Double-Stranded RNA-Dependent Protein Kinase PKR. J. Virol. 81: 11148-11158 [Abstract] [Full Text]  
  • Deas, T. S., Bennett, C. J., Jones, S. A., Tilgner, M., Ren, P., Behr, M. J., Stein, D. A., Iversen, P. L., Kramer, L. D., Bernard, K. A., Shi, P.-Y. (2007). In Vitro Resistance Selection and In Vivo Efficacy of Morpholino Oligomers against West Nile Virus. Antimicrob. Agents Chemother. 51: 2470-2482 [Abstract] [Full Text]  
  • Aguilar, P. V., Weaver, S. C., Basler, C. F. (2007). Capsid Protein of Eastern Equine Encephalitis Virus Inhibits Host Cell Gene Expression. J. Virol. 81: 3866-3876 [Abstract] [Full Text]  
  • Miller, S., Kastner, S., Krijnse-Locker, J., Buhler, S., Bartenschlager, R. (2007). The Non-structural Protein 4A of Dengue Virus Is an Integral Membrane Protein Inducing Membrane Alterations in a 2K-regulated Manner. J. Biol. Chem. 282: 8873-8882 [Abstract] [Full Text]  
  • Kinney, R. M., Huang, C. Y.-H., Whiteman, M. C., Bowen, R. A., Langevin, S. A., Miller, B. R., Brault, A. C. (2006). Avian virulence and thermostable replication of the North American strain of West Nile virus. J. Gen. Virol. 87: 3611-3622 [Abstract] [Full Text]  
  • Pijlman, G. P., Kondratieva, N., Khromykh, A. A. (2006). Translation of the Flavivirus Kunjin NS3 Gene in cis but Not Its RNA Sequence or Secondary Structure Is Essential for Efficient RNA Packaging. J. Virol. 80: 11255-11264 [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]  
  • Keller, B. C., Fredericksen, B. L., Samuel, M. A., Mock, R. E., Mason, P. W., Diamond, M. S., Gale, M. Jr. (2006). Resistance to Alpha/Beta Interferon Is a Determinant of West Nile Virus Replication Fitness and Virulence. J. Virol. 80: 9424-9434 [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]  
  • Lin, R.-J., Chang, B.-L., Yu, H.-P., Liao, C.-L., Lin, Y.-L. (2006). Blocking of Interferon-Induced Jak-Stat Signaling by Japanese Encephalitis Virus NS5 through a Protein Tyrosine Phosphatase-Mediated Mechanism.. J. Virol. 80: 5908-5918 [Abstract] [Full Text]  
  • Puig-Basagoiti, F., Tilgner, M., Forshey, B. M., Philpott, S. M., Espina, N. G., Wentworth, D. E., Goebel, S. J., Masters, P. S., Falgout, B., Ren, P., Ferguson, D. M., Shi, P.-Y. (2006). Triaryl pyrazoline compound inhibits flavivirus RNA replication.. Antimicrob. Agents Chemother. 50: 1320-1329 [Abstract] [Full Text]  
  • Miller, S., Sparacio, S., Bartenschlager, R. (2006). Subcellular Localization and Membrane Topology of the Dengue Virus Type 2 Non-structural Protein 4B. J. Biol. Chem. 281: 8854-8863 [Abstract] [Full Text]  
  • Fredericksen, B. L., Gale, M. Jr. (2006). West Nile Virus Evades Activation of Interferon Regulatory Factor 3 through RIG-I-Dependent and -Independent Pathways without Antagonizing Host Defense Signaling. J. Virol. 80: 2913-2923 [Abstract] [Full Text]  
  • Scherbik, S. V., Paranjape, J. M., Stockman, B. M., Silverman, R. H., Brinton, M. A. (2006). RNase L Plays a Role in the Antiviral Response to West Nile Virus. J. Virol. 80: 2987-2999 [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]  
  • Kajaste-Rudnitski, A., Mashimo, T., Frenkiel, M.-P., Guenet, J.-L., Lucas, M., Despres, P. (2006). The 2',5'-Oligoadenylate Synthetase 1b Is a Potent Inhibitor of West Nile Virus Replication Inside Infected Cells. J. Biol. Chem. 281: 4624-4637 [Abstract] [Full Text]  
  • Cinatl, J. Jr, Michaelis, M., Fleckenstein, C., Bauer, G., Kabickova, H., Scholz, M., Rabenau, H. F., Doerr, H. W. (2006). West Nile Virus Infection Induces Interferon Signalling in Human Retinal Pigment Epithelial Cells. IOVS 47: 645-651 [Abstract] [Full Text]  
  • Puig-Basagoiti, F., Deas, T. S., Ren, P., Tilgner, M., Ferguson, D. M., Shi, P.-Y. (2005). High-Throughput Assays Using a Luciferase-Expressing Replicon, Virus-Like Particles, and Full-Length Virus for West Nile Virus Drug Discovery. Antimicrob. Agents Chemother. 49: 4980-4988 [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]  
  • Best, S. M., Morris, K. L., Shannon, J. G., Robertson, S. J., Mitzel, D. N., Park, G. S., Boer, E., Wolfinbarger, J. B., Bloom, M. E. (2005). Inhibition of Interferon-Stimulated JAK-STAT Signaling by a Tick-Borne Flavivirus and Identification of NS5 as an Interferon Antagonist. J. Virol. 79: 12828-12839 [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]  


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