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 Spaulding, A. C.
Right arrow Articles by Rothman, A. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Spaulding, A. C.
Right arrow Articles by Rothman, A. L.

 Previous Article  |  Next Article 

Journal of Virology, January 1999, p. 398-403, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Analysis of Murine CD8+ T-Cell Clones Specific for the Dengue Virus NS3 Protein: Flavivirus Cross-Reactivity and Influence of Infecting Serotype

Anne C. Spaulding, Ichiro Kurane,dagger Francis A. Ennis, and Alan L. Rothman*

Center for Infectious Diseases and Vaccine Research, University of Massachusetts Medical Center, Worcester, Massachusetts 01655

Received 21 July 1998/Accepted 5 October 1998

Serotype-cross-reactive dengue virus-specific cytotoxic T lymphocytes (CTL) induced during a primary dengue virus infection are thought to play a role in the immunopathogenesis of dengue hemorrhagic fever (DHF) during a secondary dengue virus infection. Although there is no animal model of DHF, we previously reported that murine dengue virus-specific CTL responses are qualitatively similar to human dengue virus-specific CTL responses. We used BALB/c mice to study the specificity of the CTL response to an immunodominant epitope on the dengue virus NS3 protein. We mapped the minimal H-2Kd-restricted CTL epitope to residues 298 to 306 of the dengue type 2 virus NS3 protein. In short-term T-cell lines and clones, the predominant CD8+ CTL to this epitope in mice immunized with dengue type 2 virus or vaccinia virus expressing the dengue type 4 virus NS3 protein were cross-reactive with dengue type 2 or type 4 virus, while broadly serotype-cross-reactive CTL were a minority population. In dengue type 3 virus-immunized mice, the predominant CTL response to this epitope was broadly serotype cross-reactive. All of the dengue virus-specific CTL clones studied also recognized the homologous NS3 sequences of one or more closely related flaviviruses, such as Kunjin virus. The critical contact residues for the CTL clones with different specificities were mapped with peptides having single amino acid substitutions. These data demonstrate that primary dengue virus infection induces a complex population of flavivirus-cross-reactive NS3-specific CTL clones in mice and suggest that CTL responses are influenced by the viral serotype. These findings suggest an additional mechanism by which the order of sequential flavivirus infections may influence disease manifestations.

* Corresponding author. Mailing address: Center for Infectious Diseases and Vaccine Research, University of Massachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655. Phone: (508) 856-4182. Fax: (508) 856-4890. E-mail: alan.rothman{at}ummed.edu.

dagger Present address: Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

Journal of Virology, January 1999, p. 398-403, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Yauch, L. E., Zellweger, R. M., Kotturi, M. F., Qutubuddin, A., Sidney, J., Peters, B., Prestwood, T. R., Sette, A., Shresta, S. (2009). A Protective Role for Dengue Virus-Specific CD8+ T Cells. J. Immunol. 182: 4865-4873 [Abstract] [Full Text]  
  • Noisakran, S., Perng, G. C. (2008). Alternate Hypothesis on the Pathogenesis of Dengue Hemorrhagic Fever (DHF)/Dengue Shock Syndrome (DSS) in Dengue Virus Infection. Exp. Biol. Med. 233: 401-408 [Abstract] [Full Text]  
  • Selin, L. K., Brehm, M. A. (2007). Frontiers in Nephrology: Heterologous Immunity, T Cell Cross-Reactivity, and Alloreactivity. J. Am. Soc. Nephrol. 18: 2268-2277 [Abstract] [Full Text]  
  • Wang, T., Gao, Y., Scully, E., Davis, C. T., Anderson, J. F., Welte, T., Ledizet, M., Koski, R., Madri, J. A., Barrett, A., Yin, Z., Craft, J., Fikrig, E. (2006). {gamma}{delta} T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice. J. Immunol. 177: 1825-1832 [Abstract] [Full Text]  
  • Mitaksov, V., Fremont, D. H. (2006). Structural Definition of the H-2Kd Peptide-binding Motif. J. Biol. Chem. 281: 10618-10625 [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]  
  • Doisne, J.-M., Urrutia, A., Lacabaratz-Porret, C., Goujard, C., Meyer, L., Chaix, M.-L., Sinet, M., Venet, A. (2004). CD8+ T Cells Specific for EBV, Cytomegalovirus, and Influenza Virus Are Activated during Primary HIV Infection. J. Immunol. 173: 2410-2418 [Abstract] [Full Text]  
  • Shresta, S., Kyle, J. L., Snider, H. M., Basavapatna, M., Beatty, P. R., Harris, E. (2004). Interferon-Dependent Immunity Is Essential for Resistance to Primary Dengue Virus Infection in Mice, Whereas T- and B-Cell-Dependent Immunity Are Less Critical. J. Virol. 78: 2701-2710 [Abstract] [Full Text]  
  • Harvey, T. J., Anraku, I., Linedale, R., Harrich, D., Mackenzie, J., Suhrbier, A., Khromykh, A. A. (2003). Kunjin Virus Replicon Vectors for Human Immunodeficiency Virus Vaccine Development. J. Virol. 77: 7796-7803 [Abstract] [Full Text]  
  • Twiddy, S. S., Woelk, C. H., Holmes, E. C. (2002). Phylogenetic evidence for adaptive evolution of dengue viruses in nature. J. Gen. Virol. 83: 1679-1689 [Abstract] [Full Text]  
  • Zivna, I., Green, S., Vaughn, D. W., Kalayanarooj, S., Stephens, H. A. F., Chandanayingyong, D., Nisalak, A., Ennis, F. A., Rothman, A. L. (2002). T Cell Responses to an HLA-B*07-Restricted Epitope on the Dengue NS3 Protein Correlate with Disease Severity. J. Immunol. 168: 5959-5965 [Abstract] [Full Text]  
  • Regner, M., Lobigs, M., Blanden, R. V., Milburn, P., Mullbacher, A. (2001). Antiviral Cytotoxic T Cells Cross-Reactively Recognize Disparate Peptide Determinants from Related Viruses but Ignore More Similar Self- and Foreign Determinants. J. Immunol. 166: 3820-3828 [Abstract] [Full Text]  
  • Huang, C. Y.-H., Butrapet, S., Pierro, D. J., Chang, G.-J. J., Hunt, A. R., Bhamarapravati, N., Gubler, D. J., Kinney, R. M. (2000). Chimeric Dengue Type 2 (Vaccine Strain PDK-53)/Dengue Type 1 Virus as a Potential Candidate Dengue Type 1 Virus Vaccine. J. Virol. 74: 3020-3028 [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»