Distinct Mechanisms of CD4<sup>+</sup>and CD8<sup>+</sup>T-Cell Activation and Bystander Apoptosis Induced by Human Immunodeficiency Virus Type 1 Virions

Holm, Geoffrey H.; Gabuzda, Dana

doi:10.1128/jvi.79.10.6299-6311.2005

Cited by 88 publications

(63 citation statements)

References 91 publications

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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%

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%

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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“…Cytolysis of HIV-1-infected CD4 cells and MDMs was greater than expected from the amount of viruses used for infection and the duration of infection before various assays. It is well known that HIV-1 promotes cell death in uninfected bystander cells through multiple mechanisms [28,29], including secretion of soluble factors [30], cell-tocell fusion [31] and up-regulation of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) [32]. While our cell lysis assays might have over-estimated the extent of NK cell-mediated killing, it is highly unlikely that the uniform experimental conditions could impact cells differentially based on their P2 genotypes.…”

Section: Discussionmentioning

confidence: 99%

Dimorphic HLA-B signal peptides differentially influence HLA-E- and natural killer cell-mediated cytolysis of HIV-1-infected target cells

Merino

Sabbaj

Easlick

et al. 2013

Clinical and Experimental Immunology

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SummaryAs a mechanism of self-protection, signal peptides cleaved from human leukocyte antigen (HLA) class I products bind to HLA-E before the complex interacts with the natural killer (NK) cell receptor CD94/NKG2A to inhibit NK-mediated cell lysis. Two types of the signal peptides differ in their position 2 (P2) anchor residue, with P2-methionine (P2-M) having higher HLA-E binding affinity than P2-threonine (P2-T). All HLA-A and HLA-C molecules carry P2-M, whereas HLA-B products have either P2-M or P2-T. Epidemiological evidence suggests that P2-M is unfavourable in the context of HIV-1 infection, being associated with accelerated acquisition of HIV-1 infection in two African cohorts. To begin elucidating the functional mechanism, we studied NK-mediated killing of CD4 + T cells and monocyte-derived macrophages infected with two laboratory-adapted HIV-1 strains and two transmitted/founder (T/F) viruses. In the presence of target cells derived from individuals with the three HLA-B P2 genotypes (M/M, M/T and T/T), NK-mediated cytolysis was elevated consistently for P2-T in a dosedependent manner for all cell and virus combinations tested (P =0·008

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“…The HIV-associated immune activation is thought to contribute to the AIDS-associated T-cell depletion (12,21,22,25,30,41), and high levels of circulating activated T cells are a strong predictor of disease progression in humans (16,17,24,28,44). A biological link between chronic immune activation and increased T-cell apoptosis during HIV infection was suggested by the presence of specific perturbations of cell cycle control in T lymphocytes isolated from HIV-infected patients (4,15,33,38).…”

Section: While the Majority Of Human Immunodeficiency Virus (Hiv)-infmentioning

confidence: 99%

Perturbations of Cell Cycle Control in T Cells Contribute to the Different Outcomes of Simian Immunodeficiency Virus Infection in Rhesus Macaques and Sooty Mangabeys

Paiardini

Cervasi

Sumpter

et al. 2006

J Virol

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In contrast to human immunodeficiency virus (HIV) infection of humans and experimental simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs), SIV infection of sooty mangabeys (SMs), a natural host African monkey species, is typically nonpathogenic and associated with preservation of CD4+ T-cell counts despite chronic high levels of viral replication. In previous studies, we have shown that the lack of SIV disease progression in SMs is related to lower levels of immune activation and bystander T-cell apoptosis compared to those of pathogenic HIV/SIV infection (G. Silvestri, D. Sodora, R. Koup, M. Paiardini, S. O’Neil, H. M. McClure, S. I. Staprans, and M. B. Feinberg, Immunity 18:441-452, 2003; G. Silvestri, A. Fedanov, S. Germon, N. Kozyr, W. J. Kaiser, D. A. Garber, H. M. McClure, M. B. Feinberg, and S. I. Staprans, J. Virol. 79:4043-4054, 2005). In HIV-infected patients, increased T-cell susceptibility to apoptosis is associated with a complex cell cycle dysregulation (CCD) that involves increased activation of the cyclin B/p34-cdc2 complex and abnormal nucleolar structure with dysregulation of nucleolin turnover. Here we report that CCD is also present during pathogenic SIV infection of RMs, and its extent correlates with the level of immune activation and T-cell apoptosis. In marked contrast, naturally SIV-infected SMs show normal regulation of cell cycle control (i.e., normal intracellular levels of cyclin B and preserved nucleolin turnover) and a low propensity to apoptosis in both peripheral blood- and lymph node-derived T cells. The absence of significant CCD in the AIDS-free, non-immune-activated SMs despite high levels of viral replication indicates that CCD is a marker of disease progression during lentiviral infection and supports the hypothesis that the preservation of cell cycle control may help to confer the disease-resistant phenotype of SIV-infected SMs.

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Distinct Mechanisms of CD4⁺and CD8⁺T-Cell Activation and Bystander Apoptosis Induced by Human Immunodeficiency Virus Type 1 Virions

Abstract: Apoptosis of uninfected bystander T cells contributes to T-cell depletion during human immunodeficiency virus type 1 (HIV-1

Cited by 88 publications

References 91 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

Dimorphic HLA-B signal peptides differentially influence HLA-E- and natural killer cell-mediated cytolysis of HIV-1-infected target cells

Perturbations of Cell Cycle Control in T Cells Contribute to the Different Outcomes of Simian Immunodeficiency Virus Infection in Rhesus Macaques and Sooty Mangabeys

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Distinct Mechanisms of CD4+and CD8+T-Cell Activation and Bystander Apoptosis Induced by Human Immunodeficiency Virus Type 1 Virions

Abstract: Apoptosis of uninfected bystander T cells contributes to T-cell depletion during human immunodeficiency virus type 1 (HIV-1

Cited by 88 publications

References 91 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

Dimorphic HLA-B signal peptides differentially influence HLA-E- and natural killer cell-mediated cytolysis of HIV-1-infected target cells

Perturbations of Cell Cycle Control in T Cells Contribute to the Different Outcomes of Simian Immunodeficiency Virus Infection in Rhesus Macaques and Sooty Mangabeys

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Distinct Mechanisms of CD4⁺and CD8⁺T-Cell Activation and Bystander Apoptosis Induced by Human Immunodeficiency Virus Type 1 Virions