Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection

Leligdowicz, Aleksandra; Yindom, L M; Onyango, Clayton; Sarge-Njie, Ramu; Alabi, Abraham; Cotten, Matthew; Vincent, Tim; Costa, Carlos da Silva; Aaby, Péter; Jaye, Assan; Dong, Tao; McMichael, Andrew; Whittle, Hilton; Rowland‐Jones, Sarah

doi:10.1172/jci32380

Cited by 77 publications

(88 citation statements)

References 46 publications

(64 reference statements)

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“…The robust correlation between the viral load and immune activation in HIV-2-infected individuals strongly suggests that plasma virus is one of them. HIV virions have multiple means to promote immune activation, among which are double-stranded RNA binding to Toll-like receptors (15), binding of gp120 to cell surface receptors (11), Tat internalization by uninfected cells (12), and antigenic stimulation (17). Current studies also show that microbial translocation can be associated with immune activation in HIV-1-infected individuals independently of the viral load (13), which may also be the case in HIV-2-infected individuals.…”

Section: Vol 83 2009 Hiv-2 Nef Does Not Protect Against Disease Promentioning

confidence: 94%

“…Twenty-eight antiretroviral-naïve subjects, described in Table 1, were recruited from a community cohort in Caio, Guinea Bissau, established in 1989 (27). Plasma samples were screened for HIV antibodies and virus loads, and stabilized whole-blood samples were used for CD4 count analysis as described elsewhere (17). Subjects with HIV-1/HIV-2 dual status were excluded from the study.…”

Section: Methodsmentioning

confidence: 99%

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Downregulation of the T-Cell Receptor by Human Immunodeficiency Virus Type 2 Nef Does Not Protect against Disease Progression

Feldmann

Leligdowicz

Jaye

et al. 2009

J Virol

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Chronic immune activation is thought to play a major role in human immunodeficiency virus (HIV) pathogenesis, but the relative contributions of multiple factors to immune activation are not known. One proposed mechanism to protect against immune activation is the ability of Nef proteins from some HIV and simian immunodeficiency virus strains to downregulate the T-cell receptor (TCR)-CD3 complex of the infected cell, thereby reducing the potential for deleterious activation. HIV type 1 (HIV-1) Nef has lost this property. In contrast to HIV-1, HIV-2 infection is characterized by a marked disparity in the disease course, with most individuals maintaining a normal life span. In this study, we examined the relationship between the ability of HIV-2 Nef proteins to downregulate the TCR and immune activation, comparing progressors and nonprogressors. Representative Nef variants were isolated from 28 HIV-2-infected individuals. We assessed their abilities to downregulate the TCR from the surfaces of CD4 T cells. In the same individuals, the activation of peripheral lymphocytes was evaluated by measurement of the expression levels of HLA-DR and CD38. We observed a striking correlation of the TCR downregulation efficiency of HIV-2 Nef variants with immune activation in individuals with a low viral load. This strongly suggests that Nef expression can influence the activation state of the immune systems of infected individuals. However, the efficiency of TCR downregulation by Nef was not reduced in progressing individuals, showing that TCR downregulation does not protect against progression in HIV-2 infection.

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Section: Vol 83 2009 Hiv-2 Nef Does Not Protect Against Disease Promentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Downregulation of the T-Cell Receptor by Human Immunodeficiency Virus Type 2 Nef Does Not Protect against Disease Progression

Feldmann

Leligdowicz

Jaye

et al. 2009

J Virol

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“…Overlapping peptide sets representing entire HIV-2 Gag (n 5 70) and Env (n 5 107) proteins 11 were used for stimulations. Freshly thawed, cryopreserved PBMCs were resuspended in RPMI supplemented with 10% heat-inactivated fetal calf serum, 2 mM L-glutamine (Sigma-Aldrich), 1% PenStrep (Sigma-Aldrich) (R10), and 60 mg/mL DNase solution (Type IV, Sigma-Aldrich) for 15 minutes at 37°C.…”

Section: Intracellular Cytokine Stimulation and Polychromatic Flow Cymentioning

confidence: 99%

“…When the T-cell response toward the HIV-2 proteome was compared between these 2 groups, viral control was strongly associated with high-magnitude HIV-2 Gag-specific responses. 11 However, this study was performed using ELISpot assays that did not distinguish between CD4…”

Section: Introductionmentioning

confidence: 99%

Correlates of T-cell–mediated viral control and phenotype of CD8+ T cells in HIV-2, a naturally contained human retroviral infection

Silva

Peng

Leligdowicz

et al. 2013

Blood

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“…A large cohort study of HIV-1-infected subjects in Durban, South Africa showed that viral control was significantly associated with CTL responses towards the HIV-1 gag protein: no such relationship was seen for responses to other viral proteins [1]. A smaller study in HIV-2-infected people in West Africa, in which the demarcation between progressors and non-progressors is more striking, also showed a significant association between gag-specific responses and low viral load: in this study the relationship could be further delineated to a single 15 amino acid gag peptide in a highly conserved region of the virus [2].…”

Section: Cost-effective Hiv Diagnosismentioning

confidence: 54%

News and EFIS – Eur. J. Immunol. 1/2008

Rowland‐Jones

2007

Eur J Immunol

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This year is the 25 th anniversary of the identification of HIV and the editorial team would like to dedicate this month's News and EFIS to a reflection on HIV. First, Deborah Jack, the Chief Executive at the National AIDS Trust in the UK, highlights World AIDS Day 2007 and the need to communicate efficiently to fight against HIV. Second, Sarah Rowland-Jones, an expert in HIV research, gives us an overview of the recent advances in HIV immunology, indicating how these may contribute to the design of a successful vaccine and underlining the difficulties in developing a promising candidate.

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Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection

Cited by 77 publications

References 46 publications

Downregulation of the T-Cell Receptor by Human Immunodeficiency Virus Type 2 Nef Does Not Protect against Disease Progression

Downregulation of the T-Cell Receptor by Human Immunodeficiency Virus Type 2 Nef Does Not Protect against Disease Progression

Correlates of T-cell–mediated viral control and phenotype of CD8+ T cells in HIV-2, a naturally contained human retroviral infection

News and EFIS – Eur. J. Immunol. 1/2008

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