Decreased ability of HIV-1 Tat protein-treated accessory cells to organize cellular clusters is associated with partial activation of T cells

et al. 2002

J Biomed Sci

The ability of cells of the human monocyte/macrophage lineage to host HIV-1 replication while resisting cell death is believed to significantly contribute to their ability to serve as a reservoir for viral replication in the host. Although macrophages are generally resistant to apoptosis, interruption of anti-apoptotic pathways can render them susceptible to apoptosis. Here we report that HIV-1(BAL )infection of primary human monocyte-derived macrophages (MDM) upregulates the mRNA and protein levels of the anti-apoptic gene, Bcl-2. Furthermore, this upregulation can be quantitatively mimicked by treating MDM with soluble HIV-1 Tat-86 protein. These results suggest that in infecting cells of the monocyte/macrophage lineage, HIV-1 may be benefiting from additional protection against apoptosis caused by specific upregulation of cellular anti-apoptotic genes.

Section: Discussionmentioning

confidence: 99%

Bcl-2 upregulation by HIV-1 tat during infection of primary human macrophages in culture

et al. 2002

J Biomed Sci

“…In some systems, intracellularly produced Tat promotes apoptosis [10,20,41]. Exogenous Tat has been reported to have several effects on primary cultured monocytes including dysregulation of cytokine expression [22,53], upregulation of HIV co-receptors [13] promotion of chemotaxis and microvascular invasion [1,21,22], decreased ability to organize cellular clusters associated with partial activation of T cells [49] and antagonism of CXCR4 binding by cytokines [50]. To this list should now be added upregulation of the apoptosis inhibitor, Bcl-2.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 Upregulation by HIV-1 Tat during Infection of Primary Human Macrophages in Culture

Journal of Biomedical Science

et al. 2002

The ability of cells of the human monocyte/macrophage lineage to host HIV-1 replication while resisting cell death is believed to significantly contribute to their ability to serve as a reservoir for viral replication in the host. Although macrophages are generally resistant to apoptosis, interruption of anti-apoptotic pathways can render them susceptible to apoptosis. Here we report that HIV-1_BALinfection of primary human monocyte-derived macrophages (MDM) upregulates the mRNA and protein levels of the anti-apoptic gene, Bcl-2. Furthermore, this upregulation can be quantitatively mimicked by treating MDM with soluble HIV-1 Tat-86 protein. These results suggest that in infecting cells of the monocyte/macrophage lineage, HIV-1 may be benefiting from additional protection against apoptosis caused by specific upregulation of cellular anti-apoptotic genes.

“…In some systems, intracellularly produced Tat promotes apoptosis [5,20]. Exogenous Tat has been reported to have several effects on primary cultured monocytes, including upregulation of cytokine expression [12,23], upregulation of HIV coreceptors [16], promotion of chemotaxis and microvascular invasion [1,21,22], decreased ability to organize cellular clusters associated with partial activation of T cells [49] and antagonism of CXCR4 binding by cytokines [50]. To this list should now be added upregulation of the apoptosis inducer TRAIL.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Potential HIV-Induced Source of Bystander-Mediated Apoptosis in T Cells: Upregulation of TRAIL in Primary Human Macrophages by HIV-1 Tat

et al. 2001

J Biomed Sci

The induction of apoptosis in T cells by bystander cells has been repeatedly implicated as a mechanism contributing to the T cell depletion seen in HIV infection. It has been shown that apoptosis could be induced in T cells from asymptomatic HIV-infected individuals in a Fas-independent, TNF-related apoptosis-inducing ligand (TRAIL)-dependent manner if the cells were pretreated with anti-CD3. It has also been shown that T cells from HIV-infected patients were even more sensitive to TRAIL induction of apoptosis than they were to Fas induction. Recently, it has been reported that in an HIV-1 SCID-Hu model, the vast majority of the T cell apoptosis is not associated with p24 and is therefore produced by bystander effects. Furthermore, few apoptotic cells were associated with neighboring cells which were positive for either Fas ligand or TNF. However, most of the apoptotic cells were associated with TRAIL-positive cells. The nature of these TRAIL-positive cells was undetermined. Here, we report that HIV infection of primary human macrophages switches on abundant TRAIL production both at the RNA and protein levels. Furthermore, more macrophages produce TRAIL than are infected by HIV, indicating that a bystander mechanism may, at least in part, upregulate TRAIL. Exogenously supplied HIV-1 Tat protein upregulates TRAIL production by primary human macrophages to an extent indistinguishable from infection. The results suggest a model in which HIV-1-infected cells produce extracellular Tat protein, which in turn upregulates TRAIL in macrophages which then can induce apoptosis in bystander T cells.