TY - JOUR
T1 - Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging
AU - Leeansyah, Edwin
AU - Cameron, Paul Urquhart
AU - Solomon, Ajantha
AU - Tennakoon, Gayani Surekha
AU - Velayudham, Pushparaj
AU - Gouillou, Maelenn
AU - Spelman, Tim Denis
AU - Hearps, Anna Clare
AU - Fairley, Christopher Kit
AU - Smit, Devilliers
AU - Pierce, Anna
AU - Armishaw, Jude
AU - Crowe, Suzanne Mary
AU - Cooper, David A
AU - Koelsch, Kersten K
AU - Liu, Jun-Ping
AU - Chuah, John
AU - Lewin, Sharon R
PY - 2013
Y1 - 2013
N2 - Human immunodeficiency virus (HIV)-infected patients on combination active antiretroviral therapy (cART) are at increased risk of age-related complications. We hypothesized that nucleos(t)ide reverse transcriptase inhibitors (NRTI) may contribute to accelerated aging in HIV-infected individuals on cART via inhibition of telomerase activity.Methods. Telomerase activity and telomere length (TL) were measured by quantitative polymerase chain reaction in vitro in activated peripheral blood mononuclear cells (PBMCs) cultured with NRTI and ex vivo in PBMCs from uninfected patients exposed to NRTI and from HIV-infected patients on NRTI-containing cART.Results. Lamivudine, abacavir, zidovudine, emtricitabine, and tenofovir significantly inhibited telomerase activity in activated PBMCs in vitro. Tenofovir was the most potent inhibitor of telomerase activity and caused greatest shortening of TL in vitro at the therapeutic concentration of 0.3 ?M. PBMCs from HIV-infected patients receiving NRTI-containing cART (n = 39) had significantly lower telomerase activity than HIV-uninfected patients (n = 47; P =. 011) and HIV-infected patients receiving non-NRTI-containing cART (n = 11; P
AB - Human immunodeficiency virus (HIV)-infected patients on combination active antiretroviral therapy (cART) are at increased risk of age-related complications. We hypothesized that nucleos(t)ide reverse transcriptase inhibitors (NRTI) may contribute to accelerated aging in HIV-infected individuals on cART via inhibition of telomerase activity.Methods. Telomerase activity and telomere length (TL) were measured by quantitative polymerase chain reaction in vitro in activated peripheral blood mononuclear cells (PBMCs) cultured with NRTI and ex vivo in PBMCs from uninfected patients exposed to NRTI and from HIV-infected patients on NRTI-containing cART.Results. Lamivudine, abacavir, zidovudine, emtricitabine, and tenofovir significantly inhibited telomerase activity in activated PBMCs in vitro. Tenofovir was the most potent inhibitor of telomerase activity and caused greatest shortening of TL in vitro at the therapeutic concentration of 0.3 ?M. PBMCs from HIV-infected patients receiving NRTI-containing cART (n = 39) had significantly lower telomerase activity than HIV-uninfected patients (n = 47; P =. 011) and HIV-infected patients receiving non-NRTI-containing cART (n = 11; P
UR - http://jid.oxfordjournals.org/content/207/7/1157.full.pdf
U2 - 10.1093/infdis/jit006
DO - 10.1093/infdis/jit006
M3 - Article
VL - 207
SP - 1157
EP - 1165
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 7
ER -