Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes

Finkel, Terri H.; Tudor‐Williams, Gareth; Banda, Nirmal K.; Cotton, Mark F.; Curiel, Tyler J.; Monks, Colin R. F.; Baba, Timothy W.; Ruprecht, R. M.; Kupfer, Abraham

doi:10.1038/nm0295-129

Cited by 887 publications

(618 citation statements)

References 30 publications

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“…It is generally accepted that apoptosis is considered one of the major mechanisms of CD4 + T cell depletion in HIV-1 infected patients, which generally occurs in bystander cells (Finkel et al, 1995). The mechanisms by which HIV-1 kills uninfected cells remain to be fully Sastry et al, 1996;Westendorp et al, 1995a;Zauli et al, 1996), the molecular and biochemical pathways activated by HIV-1 Tat to induce apoptosis are controversial so far (McCloskey et al, 1997;Zauli et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Macho¹,

Calzado²,

Jiménez‐Reina³

et al. 1999

Oncogene

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The e ects of HIV-1 Tat protein on mitochondria membrane permeability and apoptosis were analysed in lymphoid cells. In this report we show that stabletransfected HIV-Tat cells are primed to undergo apoptosis upon serum withdrawal. This e ect was observed in both the Jhan T cell line and the K562 cells, the latter expressing the bcr-abl chimeric gene, which confers resistance to apoptosis induced by di erent stimuli. Using a cyto¯uorimetric approach we have determined that serum withdrawal induces a disruption of the transmembrane mitochondrial potential (Dc m ) followed by an increase of reactive oxygen species (ROS) and the subsequent DNA nuclear loss in K562-Tat cells but not in the K562-pcDNA cell line. These pre-apoptotic events were associated with the cleavage of the caspase-3, while the expression of Bcl-2, Bcl-X L and Bax proteins was not a ected by the presence of Tat. Regardless of the steady state of the Bax protein, we found that in both K562 and K562-Tat cells, this protein is located in the nucleus, but after serum withdrawal its localization was mainly in the cytoplasm. The activity of caspase-3 detected in K562-Tat cells after serum withdrawal paralleled with the mitochondria permeability transition. Nevertheless, in Jhan-Tat cells the inhibition of this caspase with the speci®c inhibitor, z-DEVD-cmk, did not a ect the disruption of the mitochondria potential induced by serum withdrawal. Interestingly, we found that HIV-Tat protein accumulates at the mitochondria in the K562-Tat cells cultured under low serum conditions, and this mitochondrial localization correlated with the Dc m disruption detected in these cells. In addition, HIV-1 Tat protein synergies with protoporphyrin IX (PPIX), a ligand of the mitochondrial benzodiazepine receptor, in the induction of apoptosis in both Jhan and K562 cells. Thus, HIV-1 Tat protein may induce apoptosis by a mechanism that involves mitochondrial PT and may contribute to the lymphocyte depletion seen in AIDS patients.

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Section: Discussionmentioning

confidence: 99%

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Macho¹,

Calzado²,

Jiménez‐Reina³

et al. 1999

Oncogene

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“…Several studies have found that abnormal levels of apoptosis occur both in vitro [41][42][43][44][45][46][47][48][49][50][51] and in vivo 52,53 in CD4 þ and CD8 þ T cells from HIV-1-infected persons. Importantly, the majority of T cells undergoing apoptosis in HIV-infected patients are not infected by the virus; 52,53 this observation led to the definition of 'bystander' apoptosis when referring to apoptosis that is not occurring as a direct cytopathic effect of HIV. Clinical studies have revealed that HIV-1 and HIV-2 differ in their natural course of infection.…”

Section: T-cell Apoptosis and Aidsmentioning

confidence: 99%

Apoptosis in SIV infection

et al. 2005

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“…During early infection, the cell destruction involves primarily CCR5+ effector memory T cells and occurs predominantly in the mucosal tissue, particularly in the intestinal immune system [15,16]. Disordered apoptosis and an increased rate of activation-induced cell death (AICD) lead to destabilization and progressive change of the homeostasis of resting naive and memory T cell populations [14,[17][18][19][20]. It is unclear, and even controversial, which of pro-apoptotic (e.g.…”

Section: Introductionmentioning

confidence: 99%

Effect of Antiretroviral Therapy on Apoptosis Markers and Morphology in Peripheral Lymph Nodes of HIV-Infected Individuals

et al. 2008

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Background: CD4+ T cell depletion and destruction and the involution of the lymphoid tissue are hallmarks of HIV infection. Although the underlying mechanisms are still unclear, apoptosis appears to play a central role. The objective of this study was to investigate the effect of antiretroviral therapy on the lymph node tissue, particularly with respect to morphology and apoptosis. Patients and Methods: Between 1997 and 1999, two inguinal lymph nodes were excised from 31 previously untreated individuals who were in an early stage of HIV infection, the first one prior to treatment and the second after 16 to 20 months of treatment. Paraffin sections were investigated for lymph node architecture, distribution of cellular and viral markers, apoptosis, and expression of apoptotic key molecules which indirectly reflect apoptotic processes.

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Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes

Cited by 887 publications

References 30 publications

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Apoptosis in SIV infection

Effect of Antiretroviral Therapy on Apoptosis Markers and Morphology in Peripheral Lymph Nodes of HIV-Infected Individuals

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