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

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

Research output: Contribution to journalArticle

59 Citations (Scopus)

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 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 Gag 181-189CM9-specific CD8+ T cells to control viral replication. However, gamma interferon (IFN-γ) enzyme-linked immunospot and IFN-γ/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.

Original languageEnglish (US)
Pages (from-to)2624-2634
Number of pages11
JournalJournal of Virology
Volume81
Issue number6
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
epitopes
Antiviral Agents
Epitopes
virus replication
T-lymphocytes
T-Lymphocytes
Virus Replication
Cell Line
cell lines
Human immunodeficiency virus
HIV
T-Cell Antigen Receptor Specificity
T-Lymphocyte Epitopes
Viral Proteins
Interferons
Interferon-gamma
viral proteins
assays

ASJC Scopus subject areas

  • Immunology

Cite this

The antiviral efficacy of simian immunodeficiency virus-specific CD8 + T cells is unrelated to epitope specificity and is abrogated by viral escape. / Loffredo, John T.; Burwitz, Benjamin; Rakasz, Eva G.; Spencer, Sean P.; Stephany, Jason J.; Vela, Juan Pablo Giraldo; Martin, Sarah R.; Reed, Jason; Piaskowski, Shari M.; Furlott, Jessica; Weisgrau, Kim L.; Rodrigues, Denise S.; Soma, Taeko; Napoé, Gnankang; Friedrich, Thomas C.; Wilson, Nancy A.; Kallas, Esper G.; Watkins, David I.

In: Journal of Virology, Vol. 81, No. 6, 03.2007, p. 2624-2634.

Research output: Contribution to journalArticle

Loffredo, JT, Burwitz, B, Rakasz, EG, Spencer, SP, Stephany, JJ, Vela, JPG, Martin, SR, Reed, J, Piaskowski, SM, Furlott, J, Weisgrau, KL, Rodrigues, DS, Soma, T, Napoé, G, Friedrich, TC, Wilson, NA, Kallas, EG & Watkins, DI 2007, 'The antiviral efficacy of simian immunodeficiency virus-specific CD8 + T cells is unrelated to epitope specificity and is abrogated by viral escape', Journal of Virology, vol. 81, no. 6, pp. 2624-2634. https://doi.org/10.1128/JVI.01912-06
Loffredo, John T. ; Burwitz, Benjamin ; Rakasz, Eva G. ; Spencer, Sean P. ; Stephany, Jason J. ; Vela, Juan Pablo Giraldo ; Martin, Sarah R. ; Reed, Jason ; Piaskowski, Shari M. ; Furlott, Jessica ; Weisgrau, Kim L. ; Rodrigues, Denise S. ; Soma, Taeko ; Napoé, Gnankang ; Friedrich, Thomas C. ; Wilson, Nancy A. ; Kallas, Esper G. ; Watkins, David I. / The antiviral efficacy of simian immunodeficiency virus-specific CD8 + T cells is unrelated to epitope specificity and is abrogated by viral escape. In: Journal of Virology. 2007 ; Vol. 81, No. 6. pp. 2624-2634.
@article{7bdf9c5c82664f7f83387703e9627553,
title = "The antiviral efficacy of simian immunodeficiency virus-specific CD8 + T cells is unrelated to epitope specificity and is abrogated by viral escape",
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 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 Gag 181-189CM9-specific CD8+ T cells to control viral replication. However, gamma interferon (IFN-γ) enzyme-linked immunospot and IFN-γ/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.",
author = "Loffredo, {John T.} and Benjamin Burwitz and Rakasz, {Eva G.} and Spencer, {Sean P.} and Stephany, {Jason J.} and Vela, {Juan Pablo Giraldo} and Martin, {Sarah R.} and Jason Reed and Piaskowski, {Shari M.} and Jessica Furlott and Weisgrau, {Kim L.} and Rodrigues, {Denise S.} and Taeko Soma and Gnankang Napo{\'e} and Friedrich, {Thomas C.} and Wilson, {Nancy A.} and Kallas, {Esper G.} and Watkins, {David I.}",
year = "2007",
month = "3",
doi = "10.1128/JVI.01912-06",
language = "English (US)",
volume = "81",
pages = "2624--2634",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "6",

}

TY - JOUR

T1 - The antiviral efficacy of simian immunodeficiency virus-specific CD8 + T cells is unrelated to epitope specificity and is abrogated by viral escape

AU - Loffredo, John T.

AU - Burwitz, Benjamin

AU - Rakasz, Eva G.

AU - Spencer, Sean P.

AU - Stephany, Jason J.

AU - Vela, Juan Pablo Giraldo

AU - Martin, Sarah R.

AU - Reed, Jason

AU - Piaskowski, Shari M.

AU - Furlott, Jessica

AU - Weisgrau, Kim L.

AU - Rodrigues, Denise S.

AU - Soma, Taeko

AU - Napoé, Gnankang

AU - Friedrich, Thomas C.

AU - Wilson, Nancy A.

AU - Kallas, Esper G.

AU - Watkins, David I.

PY - 2007/3

Y1 - 2007/3

N2 - 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 Gag 181-189CM9-specific CD8+ T cells to control viral replication. However, gamma interferon (IFN-γ) enzyme-linked immunospot and IFN-γ/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.

AB - 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 Gag 181-189CM9-specific CD8+ T cells to control viral replication. However, gamma interferon (IFN-γ) enzyme-linked immunospot and IFN-γ/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.

UR - http://www.scopus.com/inward/record.url?scp=33947414895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947414895&partnerID=8YFLogxK

U2 - 10.1128/JVI.01912-06

DO - 10.1128/JVI.01912-06

M3 - Article

VL - 81

SP - 2624

EP - 2634

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 6

ER -