HIV-1 induces in vitro up-regulation of telomerase activity in monocyte-derived macrophages

REYNOSO R., CEBALLOS A. , SABATTÉ J. , SALOMON H., QUARLERI J.

Mexico

Conferencia; XVII International AIDS Conference; 2008

Background: Macrophages are key cells involved in HIV-1 pathogenesis but the underlying mechanisms are still unclear. Different reports show that HIV-1 can down-regulate telomerase activity in peripheral blood mononuclear cells (PBMC) in vivo and in vitro. Telomerase is an enzyme involved in mechanisms that control cell life span, survival and prevention of apoptosis.  The impact of HIV-1 infection on telomerase activity on monocytes derived- macrophages (MDM) was investigated. Methods: MDM were prepared from PBMC of 7 different healthy donors. HIV-1(BAL) infection of MDM were performed and followed till 13 days after. The kinetics and efficacy of infection were evaluated by both quantitative detection of Ag p24 in culture supernatants and intracellular compartment by using EIA assay and flow cytometry, respectively. Cells were harvested and split for telomerase activity quantification (Real Time PCR). Purified recombinant Tat and gp120 proteins from the IIIB isolate as well as lipopolysaccharides (LPS) were separately added to the MDM cultures on day 0. All experiments were repeated at least by triplicate. Results: Culture maintained MDM-cells showed unaffected telomerase activity, which was increased significantly by HIV-1 (p <0.01) from 24 h after infection reaching a maximum at day 13-after infection.  The enzymatic modification was directly related to the infection efficacy, ranged from 9.5 to 57%. The telomerase activity in MDM was not changed after exposure to soluble Tat protein, gp-120 and LPS neither by exposure to UV-inactivated HIV-1 or ultra centrifuged HIV-1 infected-MDM culture supernatant.Conclusions: This study shows for the first time that HIV-1 induces up-regulation of telomerase activity in infected monocyte derived-macrophage cells, enhancing its persistence.  The effect could be related to active virus replication. This mechanism support that these cells are relatively refractory to the cytopathic effects of HIV infection compared with HIV-1-infected CD4+ T cells.