The antiviral efficacy of simian immunodeficiency virus-specific CD8(+) T cells is unrelated to epitope specificity and is abrogated by viral escape

The antiviral efficacy of simian immunodeficiency virus-specific CD8(+) T cells is unrelated to epitope specificity and is abrogated by viral escape

Author Loffredo, John T. Google Scholar
Burwitz, Benjamin J. Google Scholar
Rakasz, Eva G. Google Scholar
Spencer, Sean P. Google Scholar
Stephany, Jason J. Google Scholar
Vela, Juan Pablo Giraldo Google Scholar
Martin, Sarah R. Google Scholar
Reed, Jason Google Scholar
Piaskowski, Shari M. Google Scholar
Furlott, Jessica Google Scholar
Weisgrau, Kim L. Google Scholar
Rodrigues, Denise S. Autor UNIFESP Google Scholar
Soma, Taeko Google Scholar
Napoe, Gnankang Google Scholar
Friedrich, Thomas C. Google Scholar
Wilson, Nancy A. Google Scholar
Kallas, Esper G. Autor UNIFESP Google Scholar
Watkins, David I. Google Scholar
Institution Univ Wisconsin
Universidade Federal de São Paulo (UNIFESP)
Abstract 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 SIN 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. Tat(28-35)SL8- and Gag(181-189)CM9-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 Tat(28-35)SL8- and Gag(181-189)CM9-specifie CD8(+) T-cell lines could suppress the replication of an escaped virus. Viral escape kabrogated the abilities of Tat(28-35)SL8- and Gag(181-189)gCM9-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.
Language English
Date 2007-03-01
Published in Journal of Virology. Washington: Amer Soc Microbiology, v. 81, n. 6, p. 2624-2634, 2007.
ISSN 0022-538X (Sherpa/Romeo, impact factor)
Publisher Amer Soc Microbiology
Extent 2624-2634
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000244850800009

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