Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8<sup>+</sup>T Cells in Primary HIV-1 Infection

Cao, Jianhong; McNevin, John; Holte, Sarah; Fink, Lisa M.; Corey, Lawrence; McElrath, M. Juliana

doi:10.1128/jvi.77.12.6867-6878.2003

Cited by 145 publications

(155 citation statements)

References 37 publications

Supporting

Mentioning

140

Contrasting

Unclassified

Order By: Relevance

“…As previously proposed [29], the absence of response may result from a deficit of Vpr peptide-specific naïve T cells in this donor in agreement with observations made in mice [33]. Previous studies showed that Vpr was targeted by CD8 1 T-cells [13][14][15] in a significant portion of seropositive donors [13][14][15]. CD8 1 T-cell epitopes were found to be spread all along the protein sequence [13,14].…”

Section: Discussionsupporting

confidence: 90%

“…Interestingly, Tat 41-55 overlaps the 31-50 [11] and 39-55 regions [12] and is close to the 30-37 sequence [15]. These regions are targeted by CD8 1 T-cells in multiple donors [11,12,15]. We therefore suggested that the long fragment 30-55 could elicit both CD4 1 and CD8 1 responses and hence constitute a potential candidate for epitope-based vaccine.…”

Section: Discussionmentioning

confidence: 94%

“…In one study, approximately one third of seropositive patients exhibited a Tat-specific CD4 + T-cell response, but the fine specificity of this response was not investigated [34]. Interestingly, Tat 41-55 overlaps the 31-50 [11] and 39-55 regions [12] and is close to the 30-37 sequence [15]. These regions are targeted by CD8 1 T-cells in multiple donors [11,12,15].…”

Section: Discussionmentioning

confidence: 99%

“…Vpr impairs DC maturation and T-cell activation [10]. Both Vpr and Tat proteins could be targeted by CD8 1 T-cells in seropositive donors [11][12][13][14][15] and hence constitute potential candidates to elicit an HIV-specific cellular response. Multiple forms of Tat peptides elicit neutralizing antibodies in monkeys and lead to promising but controversial results in terms of protection [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Immunoprevalence of the CD4⁺ T‐cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively

et al. 2008

View full text Add to dashboard Cite

Recent studies have suggested including nonstructural proteins as Tat and Vpr in HIV vaccines. However, little is known about the CD4 1 T-cell response that these small proteins induce in humans. We have therefore evaluated these responses by in vitro priming experiments of CD4 1 T lymphocytes harvested in healthy donors. In the Tat protein, only one peptide primed CD4 1 T cells of eight HLA unrelated healthy donors. T cells induced by this peptide recognized immature DC loaded with the native Tat protein and are restricted by multiple HLA-DR molecules, in agreement with its binding capacity. This peptide was therefore processed in an appropriate manner and was highly immunoprevalent. CD4 1 T-cell response to Vpr peptides was more disperse and involved six different peptides depending on the HLA-DR molecules of the donors. Two overlapping peptides were T-cell stimulating in at least half of the donors. T-cell response to Vpr in multiple donors is the result of a combination of several CD4 1 T-cell epitopes with good to moderate immunoprevalence. Altogether, our results show that the frequency of responders to HIV Tat or Vpr proteins relies on one or multiple CD4 1 T-cell epitopes, respectively.Key words: CD4 1 T cells . Epitopes . HIV . HLA class II . MHC IntroductionTwenty years after the discovery of HIV, an effective prophylactic or therapeutic vaccine is still not available. Current approaches are mainly based on the introduction of structural antigens into viral vectors, their combination with strong adjuvants or their injection as DNA vaccine [1]. Alternative or complementary approaches aim at neutralizing accessory or regulatory proteins because they disturb the immune system and counteract its beneficial role [2,3]. Transacting protein (Tat) is a small regulatory protein that is expressed early in the viral cycle and is essential for viral replication [4]. Besides its transactivating activity, Tat exerts a wide range of activities. It diminishes T-cell function and provokes immunosuppression [5]. It enhances DC maturation [6] and exhibits an adjuvant activity [7]. Tat also regulates apoptosis of infected and noninfected cells by a variety of possible mechanisms including downregulation of Bcl-2 and upregulation of . In contrast to Tat, the Virus protein R (Vpr) accessory protein is expressed late in the virus cycle and is also essential for in vivo viral replication [9]. Vpr impairs DC maturation and T-cell activation [10]. Both Vpr and Tat proteins could be targeted by CD8 1 T-cells in seropositive donors [11][12][13][14][15] and hence constitute potential candidates to elicit an HIV-specific cellular response. Multiple forms of Tat peptides elicit neutralizing antibodies in monkeys and lead to promising but controversial results in terms of protection [16][17][18]. It is not known whether immune response specific for accessory or regulatory HIV proteins leads to immune escape, which has a fitness cost on the virus. Moreover, despite the requirement of CD4 1 T lymphocytes to sustain both humoral and cel...

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immunoprevalence of the CD4⁺ T‐cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively

et al. 2008

View full text Add to dashboard Cite

show abstract

“…HIV-specific CD8 ϩ cytotoxic T lymphocytes (CTL) are major contributors of immune effector activities against HIV-1. Typically, CTL are induced during acute HIV-1 infection and broaden in specificity over time (7,8,47). To date, hundreds of major histocompatibility complex (MHC) class I-restricted CTL epitopes have been identified, and each of the major HIV-1 proteins contains known epitopes (www .hiv.lanl.gov).…”

mentioning

confidence: 99%

Novel Cytotoxic T-Lymphocyte Escape Mutation by a Three-Amino-Acid Insertion in the Human Immunodeficiency Virus Type 1 p6 ^Pol and p6 ^Gag Late Domain Associated with Drug Resistance

Cao

McNevin

McSweyn

et al. 2008

J Virol

Self Cite

View full text Add to dashboard Cite

Cytolytic T lymphocytes (CTL) play a major role in controlling human immunodeficiency virus type 1 (HIV-1) infection. To evade immune pressure, HIV-1 is selected at targeted CTL epitopes, which may consequentially alter viral replication fitness. In our longitudinal investigations of the interplay between T-cell immunity and viral evolution following acute HIV-1 infection, we observed in a treatment-naïve patient the emergence of highly avid, gamma interferon-secreting, CD8 ؉ CTL recognizing an HLA-Cw*0102-restricted epitope, NSPTRREL (NL8). This epitope lies in the p6 Pol protein, located in the transframe region of the Gag-Pol polyprotein. Over the course of infection, an unusual viral escape mutation arose within the p6 Pol epitope through insertion of a 3-amino-acid repeat, NSPT(SPT)RREL, with a concomitant insertion in the p6 Gag late domain, PTAPP(APP). Interestingly, this p6 Pol insertion mutation is often selected in viruses with the emergence of antiretroviral drug resistance, while the p6 Gag late-domain PTAPP motif binds Tsg101 to permit viral budding. These results are the first to demonstrate viral evasion of immune pressure by amino acid insertions. Moreover, this escape mutation represents a novel mechanism whereby HIV-1 can alter its sequence within both the Gag and Pol proteins with potential functional consequences for viral replication and budding.

show abstract

Mechanisms of CD8⁺ T cell‐mediated suppression of HIV/SIV replication

2018

View full text Add to dashboard Cite

In this article, we summarize the role of CD8 T cells during natural and antiretroviral therapy (ART)-treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8 T cell-based HIV cure strategies. Evidence suggests that CD8 T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8 T cells is responsible for control of viremia. However, it has been proposed that CD8 T cells also use non-cytolytic mechanisms to control SIV infection. More recently, CD8 T cells were shown to be required to fully suppress virus production in ART-treated SIV-infected macaques, suggesting that CD8 T cells are involved in the control of virus transcription in latently infected cells that persist under ART. A better understanding of the complex antiviral activities of CD8 T cells during HIV/SIV infection will pave the way for immune interventions aimed at harnessing these functions to target the HIV reservoir.

show abstract

Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8⁺T Cells in Primary HIV-1 Infection

Cited by 145 publications

References 37 publications

Immunoprevalence of the CD4⁺ T‐cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively

Immunoprevalence of the CD4⁺ T‐cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively

Novel Cytotoxic T-Lymphocyte Escape Mutation by a Three-Amino-Acid Insertion in the Human Immunodeficiency Virus Type 1 p6 ^Pol and p6 ^Gag Late Domain Associated with Drug Resistance

Mechanisms of CD8⁺ T cell‐mediated suppression of HIV/SIV replication

Contact Info

Product

Resources

About

Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8+T Cells in Primary HIV-1 Infection

Cited by 145 publications

References 37 publications

Immunoprevalence of the CD4+ T‐cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively

Immunoprevalence of the CD4+ T‐cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively

Novel Cytotoxic T-Lymphocyte Escape Mutation by a Three-Amino-Acid Insertion in the Human Immunodeficiency Virus Type 1 p6 Pol and p6 Gag Late Domain Associated with Drug Resistance

Mechanisms of CD8+ T cell‐mediated suppression of HIV/SIV replication

Contact Info

Product

Resources

About

Comprehensive Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon-Secreting CD8⁺T Cells in Primary HIV-1 Infection

Immunoprevalence of the CD4⁺ T‐cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively

Immunoprevalence of the CD4⁺ T‐cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively

Novel Cytotoxic T-Lymphocyte Escape Mutation by a Three-Amino-Acid Insertion in the Human Immunodeficiency Virus Type 1 p6 ^Pol and p6 ^Gag Late Domain Associated with Drug Resistance

Mechanisms of CD8⁺ T cell‐mediated suppression of HIV/SIV replication