Inhibition of Telomerase Activity by Human Immunodeficiency Virus (HIV) Nucleos(t)ide Reverse Transcriptase Inhibitors: A Potential Factor Contributing to HIV-Associated Accelerated Aging
| العنوان: | Inhibition of Telomerase Activity by Human Immunodeficiency Virus (HIV) Nucleos(t)ide Reverse Transcriptase Inhibitors: A Potential Factor Contributing to HIV-Associated Accelerated Aging |
|---|---|
| المؤلفون: | Ajantha Solomon, De Villiers Smit, Suzanne M. Crowe, Edwin Leeansyah, Jude Armishaw, Sharon R Lewin, Anna C. Hearps, Maelenn Gouillou, John Chuah, Surekha Tennakoon, Paul U. Cameron, Jun-Ping Liu, Christopher K Fairley, Anna B. Pierce, Kersten K. Koelsch, Pushparaj Velayudham, Tim Spelman, David A. Cooper |
| المصدر: | The Journal of Infectious Diseases. 207:1157-1165 |
| بيانات النشر: | Oxford University Press (OUP), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Male, Aging, Telomerase, Time Factors, Anti-HIV Agents, Organophosphonates, HIV Infections, Emtricitabine, Deoxycytidine, Polymerase Chain Reaction, Nucleoside Reverse Transcriptase Inhibitor, Young Adult, Zidovudine, Risk Factors, immune system diseases, Abacavir, Antiretroviral Therapy, Highly Active, medicine, Humans, Immunology and Allergy, Tenofovir, Cells, Cultured, Telomere Shortening, business.industry, Adenine, HIV, virus diseases, Lamivudine, Middle Aged, Telomere, Virology, Dideoxynucleosides, Reverse transcriptase, Enzyme Activation, Infectious Diseases, Case-Control Studies, Leukocytes, Mononuclear, Regression Analysis, Reverse Transcriptase Inhibitors, Female, business, medicine.drug |
| الوصف: | Background. 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 卮 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 < .001). TL was significantly inversely associated with age (P = .009) and the total duration on any NRTI (P = .01). Conclusions. NRTIs and, specifically tenofovir at therapeutic concentrations, inhibit telomerase activity leading to accelerated shortening of TL in activated PBMCs. The relationship between NRTI, reduced telomerase activity, and accelerated aging requires further investigation in HIV-infected individuals on cART. |
| تدمد: | 1537-6613 0022-1899 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6e427bdd8f7ddd427208b18e9d20da3 https://doi.org/10.1093/infdis/jit006 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f6e427bdd8f7ddd427208b18e9d20da3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15376613 00221899 |
|---|