Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging

Edwin Leeansyah, Paul Urquhart Cameron, Ajantha Solomon, Gayani Surekha Tennakoon, Pushparaj Velayudham, Maelenn Gouillou, Tim Denis Spelman, Anna Clare Hearps, Christopher Kit Fairley, Devilliers Smit, Anna Pierce, Jude Armishaw, Suzanne Mary Crowe, David A Cooper, Kersten K Koelsch, Jun-Ping Liu, John Chuah, Sharon R Lewin

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Abstract

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
Original languageEnglish
Pages (from-to)1157 - 1165
Number of pages9
JournalJournal of Infectious Diseases
Volume207
Issue number7
DOIs
Publication statusPublished - 2013

Cite this

Leeansyah, Edwin ; Cameron, Paul Urquhart ; Solomon, Ajantha ; Tennakoon, Gayani Surekha ; Velayudham, Pushparaj ; Gouillou, Maelenn ; Spelman, Tim Denis ; Hearps, Anna Clare ; Fairley, Christopher Kit ; Smit, Devilliers ; Pierce, Anna ; Armishaw, Jude ; Crowe, Suzanne Mary ; Cooper, David A ; Koelsch, Kersten K ; Liu, Jun-Ping ; Chuah, John ; Lewin, Sharon R. / Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging. In: Journal of Infectious Diseases. 2013 ; Vol. 207, No. 7. pp. 1157 - 1165.
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title = "Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging",
abstract = "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",
author = "Edwin Leeansyah and Cameron, {Paul Urquhart} and Ajantha Solomon and Tennakoon, {Gayani Surekha} and Pushparaj Velayudham and Maelenn Gouillou and Spelman, {Tim Denis} and Hearps, {Anna Clare} and Fairley, {Christopher Kit} and Devilliers Smit and Anna Pierce and Jude Armishaw and Crowe, {Suzanne Mary} and Cooper, {David A} and Koelsch, {Kersten K} and Jun-Ping Liu and John Chuah and Lewin, {Sharon R}",
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doi = "10.1093/infdis/jit006",
language = "English",
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pages = "1157 -- 1165",
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Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging. / Leeansyah, Edwin; Cameron, Paul Urquhart; Solomon, Ajantha; Tennakoon, Gayani Surekha; Velayudham, Pushparaj; Gouillou, Maelenn; Spelman, Tim Denis; Hearps, Anna Clare; Fairley, Christopher Kit; Smit, Devilliers; Pierce, Anna; Armishaw, Jude; Crowe, Suzanne Mary; Cooper, David A; Koelsch, Kersten K; Liu, Jun-Ping; Chuah, John; Lewin, Sharon R.

In: Journal of Infectious Diseases, Vol. 207, No. 7, 2013, p. 1157 - 1165.

Research output: Contribution to journalArticleResearchpeer-review

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 -