To kill or be killed: how HIV exhausts the immune system

Gougeon, M.

doi:10.1038/sj.cdd.4401616

Cited by 40 publications

(42 citation statements)

References 131 publications

(118 reference statements)

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Section: Mitochondrial Membrane Potential and Apoptosissupporting

confidence: 93%

“…The percentage of apoptotic PBMC detected by Annexin V staining was significantly higher in HIVinfected patients than in HIV-negative controls. This is in accordance with previous studies showing increased apoptosis of PBMC using different markers of apoptosis [38,39].For the first time we could demonstrate a highly significant negative correlation between the DC m and the percentage of apoptotic PBMC in HIV-infected, therapy-naïve patients: more PBMC were apoptotic when DC m was reduced. This could be seen in HIV-positive and HIV-negative study participants, but was more pronounced under HIV infection.…”

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confidence: 92%

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Mitochondrial membrane potential and apoptosis of blood mononuclear cells in untreated HIV‐1 infected patients

et al. 2009

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ObjectivesInfection with HIV leads to progressive CD4 T-cell loss, resulting in AIDS. Apoptosis is the main mechanism for the loss of infected and bystander cells, but the complex interacting factors inducing and inhibiting apoptosis are not fully understood. Mitochondrial dysfunction is a pivotal step of the apoptotic cascade and can result in reduced mitochondrial membrane potential. MethodsThe mitochondrial membrane potential of peripheral blood mononuclear cells (PBMC) was measured by flow cytometry using the dye JC-1 (Molecular Probes Inc). Apoptotic cells were identified using the Annexin V assay (Becton Dickinson GmbH). ResultsThe mitochondrial membrane potential of PBMC was significantly decreased and apoptotic cell rate was increased in HIV-infected therapy-naïve patients compared with HIV-negative controls. There was a highly significant correlation between the mitochondrial membrane potential and the rate of apoptosis. CD4 cell count was correlated negatively to the apoptotic rate and positively to the mitochondrial membrane potential. ConclusionsThe JC-1 assay is a sensitive tool to detect changes of mitochondrial membrane potential associated with apoptosis in HIV-infected therapy-naïve patients. We could show in vivo that a reduction of mitochondrial membrane potential is correlated to apoptosis of PBMC, CD4 cell count and HIV viral load during HIV infection. IntroductionInfection with HIV leads to progressive CD4 T-cell death, resulting in the development of AIDS. The mechanisms triggering this CD4 T-cell death are still not understood fully, but data indicate that apoptosis plays a major role [1]. There is a correlation between the extent of apoptosis and disease progression [2,3], and highly active antiretroviral therapy is associated with a lower level of CD4 T-cell apoptosis in HIV-1 infected patients [4][5][6][7].Both infected and uninfected CD4 T-cells can die during HIV-1 infection by different cell death pathways, but HIV-1 induced bystander CD4 T-cell demise is now recognized as pivotal to the development of immunodeficiency. Chronically increased activation of the immune system may contribute directly to progressive CD4 T-cell depletion, irrespective of viral load [8,9]. Upon receiving a death signal, a cascade of molecular events resulting in the activation or inactivation of numerous cellular proteins is initiated, leading to morphological and biochemical changes such as plasma membrane blebbing, DNA fragmentation and mitochondrial dysfunction. The regulators of the apoptotic pathway exert their function primarily at the mitochondrion by either preventing or inducing mitochondrial dysfunction [10,11]. Furthermore, there is evidence that resistance to apoptosis in persistently infected cells involves direct modulation of the mitochondrial pathway [1]. The measurement of the mitochondrial membrane potential of peripheral blood mononuclear cells (PBMC) might be a useful tool to [24]. In the early stages of apoptosis, there are changes at the cell surface. One of these plasma membrane al...

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Section: Mitochondrial Membrane Potential and Apoptosissupporting

confidence: 93%

supporting

confidence: 92%

Mitochondrial membrane potential and apoptosis of blood mononuclear cells in untreated HIV‐1 infected patients

et al. 2009

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confidence: 99%

“…3 HIV is particularly malicious since it primarily infects cells from the cognate and innate immune systems (in particular, CD4 þ T cells and monocytes), in which it manipulates apoptosis through direct effects. 3 In addition, HIV uses cell-exposed proteins (such as the Envelope glycoprotein complex, Env) 4 or secreted proteins including Vpr to induce cell death in a variety of different cell types. 5 To kill cells, HIV profoundly influences the cell biology, including the cytoskeleton, 6 by acting on multiple cellular receptors, not only the classical HIV-1 receptor CD4 with its chemokine coreceptor.…”

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confidence: 99%

“…[8][9][10] Although the detailed mechanisms accounting for T-cell death in vivo are not known, HIV-1 infection profoundly influences the T-cell repertoire, both in CD4 þ and in CD8 þ T cells in vivo. 3 Animal models such as the infection of macaques by simian immunodeficiency virus (SIV) may be important for the elucidation of the exact molecular mechanisms of the apoptotic pathways participating in the pathogenesis of AIDS.…”

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confidence: 99%

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