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 Loffredo, J. T.
Right arrow Articles by Watkins, D. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Loffredo, J. T.
Right arrow Articles by Watkins, D. I.

 Previous Article  |  Next Article 

Journal of Virology, March 2007, p. 2624-2634, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.01912-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Antiviral Efficacy of Simian Immunodeficiency Virus-Specific CD8+ T Cells Is Unrelated to Epitope Specificity and Is Abrogated by Viral Escape{triangledown}

John T. Loffredo,1 Benjamin J. Burwitz,1 Eva G. Rakasz,1 Sean P. Spencer,1 Jason J. Stephany,1 Juan Pablo Giraldo Vela,1,2 Sarah R. Martin,2 Jason Reed,1 Shari M. Piaskowski,2 Jessica Furlott,1 Kim L. Weisgrau,1 Denise S. Rodrigues,1,3 Taeko Soma,1 Gnankang Napoé,1 Thomas C. Friedrich,1 Nancy A. Wilson,1 Esper G. Kallas,3 and David I. Watkins1,2*

Wisconsin National Primate Research Center,1 Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53715,2 Division of Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil3

Received 1 September 2006/ Accepted 16 December 2006

CD8+ T lymphocytes appear to play a role in controlling human immunodeficiency virus (HIV) replication, yet routine immunological assays do not measure the antiviral efficacy of these cells. Furthermore, it has been suggested that CD8+ T cells that recognize epitopes derived from proteins expressed early in the viral replication cycle can be highly efficient. We used a functional in vitro assay to assess the abilities of different epitope-specific CD8+ T-cell lines to control simian immunodeficiency virus (SIV) replication. We compared the antiviral efficacies of 26 epitope-specific CD8+ T-cell lines directed against seven SIV epitopes in Tat, Nef, Gag, Env, and Vif that were restricted by either Mamu-A*01 or Mamu-A*02. Suppression of SIV replication varied depending on the epitope specificities of the CD8+ T cells and was unrelated to whether the targeted epitope was derived from an early or late viral protein. Tat28-35SL8- and Gag181-189CM9-specific CD8+ T-cell lines were consistently superior at suppressing viral replication compared to the other five SIV-specific CD8+ T-cell lines. We also investigated the impact of viral escape on antiviral efficacy by determining if Tat28-35SL8- and Gag181-189CM9-specific CD8+ T-cell lines could suppress the replication of an escaped virus. Viral escape abrogated the abilities of Tat28-35SL8- and Gag181-189CM9-specific CD8+ T cells to control viral replication. However, gamma interferon (IFN-{gamma}) enzyme-linked immunospot and IFN-{gamma}/tumor necrosis factor alpha intracellular-cytokine-staining assays detected cross-reactive immune responses against the Gag escape variant. Understanding antiviral efficacy and epitope variability, therefore, will be important in selecting candidate epitopes for an HIV vaccine.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Wisconsin—Madison, 555 Science Dr., Madison, WI 53711. Phone: (608) 265-3380. Fax: (608) 265-8084. E-mail: watkins{at}primate.wisc.edu.

{triangledown} Published ahead of print on 27 December 2006.

Journal of Virology, March 2007, p. 2624-2634, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.01912-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bimber, B. N., Burwitz, B. J., O'Connor, S., Detmer, A., Gostick, E., Lank, S. M., Price, D. A., Hughes, A., O'Connor, D. (2009). Ultradeep Pyrosequencing Detects Complex Patterns of CD8+ T-Lymphocyte Escape in Simian Immunodeficiency Virus-Infected Macaques. J. Virol. 83: 8247-8253 [Abstract] [Full Text]  
  • Wilson, N. A., Keele, B. F., Reed, J. S., Piaskowski, S. M., MacNair, C. E., Bett, A. J., Liang, X., Wang, F., Thoryk, E., Heidecker, G. J., Citron, M. P., Huang, L., Lin, J., Vitelli, S., Ahn, C. D., Kaizu, M., Maness, N. J., Reynolds, M. R., Friedrich, T. C., Loffredo, J. T., Rakasz, E. G., Erickson, S., Allison, D. B., Piatak, M. Jr., Lifson, J. D., Shiver, J. W., Casimiro, D. R., Shaw, G. M., Hahn, B. H., Watkins, D. I. (2009). Vaccine-Induced Cellular Responses Control Simian Immunodeficiency Virus Replication after Heterologous Challenge. J. Virol. 83: 6508-6521 [Abstract] [Full Text]  
  • Burwitz, B. J., Pendley, C. J., Greene, J. M., Detmer, A. M., Lhost, J. J., Karl, J. A., Piaskowski, S. M., Rudersdorf, R. A., Wallace, L. T., Bimber, B. N., Loffredo, J. T., Cox, D. G., Bardet, W., Hildebrand, W., Wiseman, R. W., O'Connor, S. L., O'Connor, D. H. (2009). Mauritian Cynomolgus Macaques Share Two Exceptionally Common Major Histocompatibility Complex Class I Alleles That Restrict Simian Immunodeficiency Virus-Specific CD8+ T Cells. J. Virol. 83: 6011-6019 [Abstract] [Full Text]  
  • Loffredo, J. T., Sidney, J., Bean, A. T., Beal, D. R., Bardet, W., Wahl, A., Hawkins, O. E., Piaskowski, S., Wilson, N. A., Hildebrand, W. H., Watkins, D. I., Sette, A. (2009). Two MHC Class I Molecules Associated with Elite Control of Immunodeficiency Virus Replication, Mamu-B*08 and HLA-B*2705, Bind Peptides with Sequence Similarity. J. Immunol. 182: 7763-7775 [Abstract] [Full Text]  
  • Kattan, T., MacNamara, A., Rowan, A. G., Nose, H., Mosley, A. J., Tanaka, Y., Taylor, G. P., Asquith, B., Bangham, C. R. M. (2009). The Avidity and Lytic Efficiency of the CTL Response to HTLV-1. J. Immunol. 182: 5723-5729 [Abstract] [Full Text]  
  • Bimber, B. N., Moreland, A. J., Wiseman, R. W., Hughes, A. L., O'Connor, D. H. (2008). Complete Characterization of Killer Ig-Like Receptor (KIR) Haplotypes in Mauritian Cynomolgus Macaques: Novel Insights into Nonhuman Primate KIR Gene Content and Organization. J. Immunol. 181: 6301-6308 [Abstract] [Full Text]  
  • Reynolds, M. R., Weiler, A. M., Weisgrau, K. L., Piaskowski, S. M., Furlott, J. R., Weinfurter, J. T., Kaizu, M., Soma, T., Leon, E. J., MacNair, C., Leaman, D. P., Zwick, M. B., Gostick, E., Musani, S. K., Price, D. A., Friedrich, T. C., Rakasz, E. G., Wilson, N. A., McDermott, A. B., Boyle, R., Allison, D. B., Burton, D. R., Koff, W. C., Watkins, D. I. (2008). Macaques vaccinated with live-attenuated SIV control replication of heterologous virus. JEM 205: 2537-2550 [Abstract] [Full Text]  
  • Simons, B. C., VanCompernolle, S. E., Smith, R. M., Wei, J., Barnett, L., Lorey, S. L., Meyer-Olson, D., Kalams, S. A. (2008). Despite Biased TRBV Gene Usage against a Dominant HLA B57-Restricted Epitope, TCR Diversity Can Provide Recognition of Circulating Epitope Variants. J. Immunol. 181: 5137-5146 [Abstract] [Full Text]  
  • Maness, N. J., Yant, L. J., Chung, C., Loffredo, J. T., Friedrich, T. C., Piaskowski, S. M., Furlott, J., May, G. E., Soma, T., Leon, E. J., Wilson, N. A., Piontkivska, H., Hughes, A. L., Sidney, J., Sette, A., Watkins, D. I. (2008). Comprehensive Immunological Evaluation Reveals Surprisingly Few Differences between Elite Controller and Progressor Mamu-B*17-Positive Simian Immunodeficiency Virus-Infected Rhesus Macaques. J. Virol. 82: 5245-5254 [Abstract] [Full Text]  
  • Loffredo, J. T., Bean, A. T., Beal, D. R., Leon, E. J., May, G. E., Piaskowski, S. M., Furlott, J. R., Reed, J., Musani, S. K., Rakasz, E. G., Friedrich, T. C., Wilson, N. A., Allison, D. B., Watkins, D. I. (2008). Patterns of CD8+ Immunodominance May Influence the Ability of Mamu-B*08-Positive Macaques To Naturally Control Simian Immunodeficiency Virus SIVmac239 Replication. J. Virol. 82: 1723-1738 [Abstract] [Full Text]  
  • Valentine, L. E., Piaskowski, S. M., Rakasz, E. G., Henry, N. L., Wilson, N. A., Watkins, D. I. (2008). Recognition of Escape Variants in ELISPOT Does Not Always Predict CD8+ T-Cell Recognition of Simian Immunodeficiency Virus-Infected Cells Expressing the Same Variant Sequences. J. Virol. 82: 575-581 [Abstract] [Full Text]  
  • Liu, Y., McNevin, J., Zhao, H., Tebit, D. M., Troyer, R. M., McSweyn, M., Ghosh, A. K., Shriner, D., Arts, E. J., McElrath, M. J., Mullins, J. I. (2007). Evolution of Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitopes: Fitness-Balanced Escape. J. Virol. 81: 12179-12188 [Abstract] [Full Text]  
  • Sacha, J. B., Chung, C., Reed, J., Jonas, A. K., Bean, A. T., Spencer, S. P., Lee, W., Vojnov, L., Rudersdorf, R., Friedrich, T. C., Wilson, N. A., Lifson, J. D., Watkins, D. I. (2007). Pol-Specific CD8+ T Cells Recognize Simian Immunodeficiency Virus-Infected Cells Prior to Nef-Mediated Major Histocompatibility Complex Class I Downregulation. J. Virol. 81: 11703-11712 [Abstract] [Full Text]  
  • Mandl, J. N., Regoes, R. R., Garber, D. A., Feinberg, M. B. (2007). Estimating the Effectiveness of Simian Immunodeficiency Virus-Specific CD8+ T Cells from the Dynamics of Viral Immune Escape. J. Virol. 81: 11982-11991 [Abstract] [Full Text]  
  • Kwissa, M., Amara, R. R., Robinson, H. L., Moss, B., Alkan, S., Jabbar, A., Villinger, F., Pulendran, B. (2007). Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus. JEM 204: 2733-2746 [Abstract] [Full Text]  
  • Maness, N. J., Valentine, L. E., May, G. E., Reed, J., Piaskowski, S. M., Soma, T., Furlott, J., Rakasz, E. G., Friedrich, T. C., Price, D. A., Gostick, E., Hughes, A. L., Sidney, J., Sette, A., Wilson, N. A., Watkins, D. I. (2007). AIDS virus specific CD8+ T lymphocytes against an immunodominant cryptic epitope select for viral escape. JEM 204: 2505-2512 [Abstract] [Full Text]  
  • Loffredo, J. T., Maxwell, J., Qi, Y., Glidden, C. E., Borchardt, G. J., Soma, T., Bean, A. T., Beal, D. R., Wilson, N. A., Rehrauer, W. M., Lifson, J. D., Carrington, M., Watkins, D. I. (2007). Mamu-B*08-Positive Macaques Control Simian Immunodeficiency Virus Replication. J. Virol. 81: 8827-8832 [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»