Molecular mechanisms involved in HIV-1-Tat mediated inhibition of telomerase activity in human CD4(+) T lymphocytes.

Mol Immunol 2013 Jun 31;54(2):181-92. Epub 2012 Dec 31.

Department of System Medicine, Pharmacology Section, University of Rome Tor Vergata, Rome, Italy.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2012.12.003DOI Listing
June 2013

Publication Analysis

Top Keywords

cd4+ cells
16
telomerase activity
12
nuclear import
8
phosphorylation nuclear
8
replicative potential
8
mechanisms involved
8
cd4+
6
telomerase
5
chaperones required
4
enzyme activated
4
antigenic stimulation
4
required htert
4
stimulation enzyme
4
activated post-translational
4
post-translational modifications
4
import catalytic
4
molecular interaction
4
catalytic subunit
4
cd4+ cell
4
cell expansion
4

Similar Publications