کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2831160 1163782 2013 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular mechanisms involved in HIV-1-Tat mediated inhibition of telomerase activity in human CD4+ T lymphocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Molecular mechanisms involved in HIV-1-Tat mediated inhibition of telomerase activity in human CD4+ T lymphocytes
چکیده انگلیسی

Human immunodeficiency virus type 1 (HIV-1) infection is characterized by a progressive decline of CD4+ T cells and by other immune disorders that are similar to those observed during aging and which lead eventually to AIDS. One of the mechanisms involved in HIV-1 induced immunodeficiency may be the lack of telomerase induction and the consequent impairment of the potential required for CD4+ T cell expansion. Telomerase compensates for the progressive telomere loss during cell division and preserves the replicative potential of T lymphocytes after repeated antigenic stimulation. The enzyme is activated by post-translational modifications, such as phosphorylation and also by the nuclear import of its catalytic subunit hTERT from the cytoplasm. In previous studies we found a reduction of telomerase activity in the nucleus of CD4+ T cells infected with HIV-1 or non-infected but exposed to Tat protein. However, the mechanism for this loss of activity has not been elucidated yet. In the present study, we found that HIV-1 Tat inhibited telomerase activity in CD4+ T cells by different mechanisms. First, it reduced nuclear levels of hTERT. Secondly, this protein perturbed the AKT pathway and the molecular interaction with the chaperones required for hTERT phosphorylation, nuclear import and activation. These results suggest that in addition to inducing direct cell death, HIV infection may also reduce the replicative potential of non-infected CD4+ T cells and this may contribute to the overall immunodeficiency in AIDS patients.


► Telomerase preserves the replicative potential of T cells.
► HIV-1-Tat inhibits telomerase and impairs replicative potential of CD4+ T cells.
► We studied the mechanism underlying Tat mediated inhibition of telomerase.
► Tat reduced telomerase activity by impairing AKT pathway and hTERT phosphorylation.
► Tat contributes to the aging phenotype of the immune system of HIV infected people.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 54, Issue 2, June 2013, Pages 181–192
نویسندگان
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