Sequence homology between HIV-1 gp120 and the apoptosis mediating protein Fas

Szawlowski, P.; Hanke, Thomas; Randall, R. E.

doi:10.1097/00002030-199307000-00019

Cited by 24 publications

(10 citation statements)

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“…These observations fail to explain, however, why in some cases both CD4+ and CD8+ T cells have been found to undergo apoptosis. The possibility that anti-HIV gpl20 antibodies might cross-react with the Fas protein, thereby inducing apoptosis, has also been raised (35). It is also possible that PBMCs from HIV-infected people are more susceptible to ex vivo apoptosis because the lymphocytes are chronically activated, manifestations of which include spontaneous proliferation, expression of cell surface activation markers, increased cytokine expression, and autoimmune phenomena (29).…”

Section: Resultsmentioning

confidence: 99%

Retinoic acid inhibition of ex vivo human immunodeficiency virus-associated apoptosis of peripheral blood cells.

Yang

Bailey

Vacchio

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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T cells from human immunodeficiency virus (HIV)-infected individuals undergo spontaneous and activation-induced ex vivo apoptosis. Here we report that peripheral blood mononuclear cells (PBMCs) obtained from six HIVinfected individuals exhibited reduced ex vivo DNA fragmentation and cell death after ingestion of all-trans-retinoic acid (tRA). These effects were attenuated with continued daily RA administration, which correlated with a >5-fold decrease in serum peak RA concentrations. Incubation of PBMCs from HIV+ individuals with tRA in vitro resulted in decreased DNA

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Section: Resultsmentioning

confidence: 99%

Retinoic acid inhibition of ex vivo human immunodeficiency virus-associated apoptosis of peripheral blood cells.

Yang

Bailey

Vacchio

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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“…Some of these autoantibodies may reflect crossreactivity between antibodies against viral proteins such as gp120 and cellular proteins. HIV-1 gp120 has been found to bear sequence homology to CD95 and CD4 (Szawlowski et al, 1993;Zagury et al, 1993). The identical eight amino acid sequence shared by gp120 and CD95 may be responsible for the generation of autoantibodies that react to CD95 on the surface of CD95-expressing T cells.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, gp120 has homologies to CD4 and MHC class I molecules and autoantibodies against both self proteins have been detected in sera from HIV-1 infected individuals (Zagury et al, 1993). Likewise, a sequence identity of eight aminoacids between the V3-loop of gp120 and the extracellular part of the CD95 receptor has been described (Szawlowski et al, 1993). Therefore, we reasoned that crossreactive antibodies directed against CD95 are generated during the immune response to HIV-1 and might contribute to disease progression by inducing apoptosis in CD95-positive andsensitive T cells.…”

Section: Introductionmentioning

confidence: 95%

Anti-CD95 (APO-1/Fas) autoantibodies and T cell depletion in human immunodeficiency virus Type 1 (HIV-1)-infected children

et al. 1998

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Advanced stages of HIV-1-infection are characterized by progressive CD4 + T cell depletion. Peripheral T cells from HIV-1 + donors show accelerated apoptosis in vitro. The CD95 (APO-1/Fas) receptor/ligand system is involved in this process. To further study deregulation of the CD95 system in peripheral T cells during HIV-1-infection, we measured CD95-expression on CD4 + and CD8 + T cells together with serum levels of soluble CD95 (sCD95) and anti-CD95 autoantibodies in HIV-1 + children and healthy controls. Anti-CD95 levels in HIV-1 + children were significantly elevated when compared to uninfected controls, whereas serum levels of sCD95 were not different. In HIV-1 + children, CD95-expression on CD4 + and CD8 + T cells increased with age. A strong correlation between depletion of CD4 + cells in vivo and increase in CD95-expression on CD4 + T cells was observed. In contrast, such a correlation was not found for CD8 + T cells. A negative correlation between anti-CD95 autoantibody levels and CD4 + T cell counts, that was predicted by multiple linear regression analysis of pooled data, was found in individual patients observed longitudinally by repeated measurements. Since anti-CD95 autoantibodies isolated from HIV-infected adults have previously been shown to induce apoptosis of sensitive target cells in vitro, we speculate that the interaction of these antibodes with CD95-positive and CD95-sensitive T cells in vivo might be involved in progressive T cell loss during HIV-1-infection.

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“…Apoptosis of lymphoid cells is a common finding in HIV-infected patients [29][30][31]. HIV-1 envelope protein has been shown to have a sequence homology with the apoptosis-mediat ing protein, Fas [32]. It has been suggested that HIV-1 envelope gp protein may be acting as a superantigen for the induction of apoptosis [32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

“…HIV-1 envelope protein has been shown to have a sequence homology with the apoptosis-mediat ing protein, Fas [32]. It has been suggested that HIV-1 envelope gp protein may be acting as a superantigen for the induction of apoptosis [32][33][34][35]. Recently, the occur rence of apoptosis was demonstrated in renal tissue ob tained from patients with HIV infection [11].…”

Section: Discussionmentioning

confidence: 99%

HIV-1 gp160 Envelope Protein Modulates Proliferation and Apoptosis in Mesangial Cells

Singhal

Sharma

Reddy

et al. 1997

Nephron

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Mesangial cell (MC) hyperplasia and accumulation of extracellular matrix are the predominant features of HIV-associated nephropathy (HIVAN). Since mice transgenic for HIV-1 genes show renal lesions mimicking HIVAN, we studied the effect of HIV-1 gpl60 protein on cultured murine MC (MMC) proliferation and apoptosis. HIV-1 gp160 protein stimulated (p < 0.001) MMC proliferation when compared with control MMCs. This effect of gpl60 protein peaked at a concentration of 0.01 μg/ml. MMCs treated with a higher concentration of gpl60 protein (0.1 μg/ml) or for a prolonged period of time (72 h) showed apoptosis rather than cell proliferation. These studies were further confirmed by DNA fragmentation and end labeling assays. Gp160 also enhanced apoptosis in human MCs. Tumor necrosis factor (TNF)-α enhanced (p < 0.001) MMC apoptosis, and anti-TNF-α antibodies inhibited gp160-induced MMC apoptosis. In addition, gp160 protein attenuated MMC expression of Bcl-2 mRNA expression. These results suggest that gp160-induced apoptosis may be affected in part by the release of TNF-α and associated with attenuated mRNA expression of Bcl-2 by MMCs.

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Sequence homology between HIV-1 gp120 and the apoptosis mediating protein Fas

Cited by 24 publications

References 0 publications

Retinoic acid inhibition of ex vivo human immunodeficiency virus-associated apoptosis of peripheral blood cells.

Retinoic acid inhibition of ex vivo human immunodeficiency virus-associated apoptosis of peripheral blood cells.

Anti-CD95 (APO-1/Fas) autoantibodies and T cell depletion in human immunodeficiency virus Type 1 (HIV-1)-infected children

HIV-1 gp160 Envelope Protein Modulates Proliferation and Apoptosis in Mesangial Cells

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