HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study.
The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The present report focuses on lamin A processing, a pathway known to be altered in systemic genetic progeroid syndromes.35 HIV-1 infected patients bein...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3532351?pdf=render |
| _version_ | 1818013885145284608 |
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| author | Sophie Perrin Jonathan Cremer Olivia Faucher Jacques Reynes Pierre Dellamonica Joëlle Micallef Caroline Solas Bruno Lacarelle Charlotte Stretti Elise Kaspi Andrée Robaglia-Schlupp Corinne Nicolino-Brunet Catherine Tamalet Nicolas Lévy Isabelle Poizot-Martin Pierre Cau Patrice Roll |
| author_facet | Sophie Perrin Jonathan Cremer Olivia Faucher Jacques Reynes Pierre Dellamonica Joëlle Micallef Caroline Solas Bruno Lacarelle Charlotte Stretti Elise Kaspi Andrée Robaglia-Schlupp Corinne Nicolino-Brunet Catherine Tamalet Nicolas Lévy Isabelle Poizot-Martin Pierre Cau Patrice Roll |
| author_sort | Sophie Perrin |
| collection | DOAJ |
| description | The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The present report focuses on lamin A processing, a pathway known to be altered in systemic genetic progeroid syndromes.35 HIV-1 infected patients being treated with first line antiretroviral therapy (ART, mean duration at inclusion: 2.7±1.3 years) containing boosted protease inhibitors (PI/r) (comprising lopinavir/ritonavir in 65% of patients) were recruited together with 49 seronegative age- and sex-matched control subjects (http://clinicaltrials.gov/, NCT01038999). In more than 88% of patients, the viral load was <40 copies/ml and the CD4+ cell count was >500/mm³. Prelamin A processing in peripheral blood mononuclear cells (PBMCs) from patients and controls was analysed by western blotting at inclusion. PBMCs from patients were also investigated at 12 and 24 months after enrolment in the study. PBMCs from healthy controls were also incubated with boosted lopinavir in culture medium containing various concentrations of proteins (4 to 80 g/L).Lamin A precursor was not observed in cohort patient PBMC regardless of the PI/r used, the dose and the plasma concentration. Prelamin A was detected in PBMC incubated in culture medium containing a low protein concentration (4 g/L) but not in plasma (60-80 g/L) or in medium supplemented with BSA (40 g/L), both of which contain a high protein concentration.Prelamin A processing abnormalities were not observed in PBMCs from patients under the PI/r first line regimen. Therefore, PI/r do not appear to contribute to lamin A-related aging in PBMCs. In cultured PBMCs from healthy donors, prelamin A processing abnormalities were only observed when the protein concentration in the culture medium was low, thus increasing the amount of PI available to enter cells. ClinicalTrials.gov NCT01038999 http://clinicaltrials.gov/ct2/show/NCT01038999. |
| first_indexed | 2024-04-14T06:38:49Z |
| format | Article |
| id | doaj.art-f10f2f65b8fd4eda9018332af527c623 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T06:38:49Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-f10f2f65b8fd4eda9018332af527c6232022-12-22T02:07:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5303510.1371/journal.pone.0053035HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study.Sophie PerrinJonathan CremerOlivia FaucherJacques ReynesPierre DellamonicaJoëlle MicallefCaroline SolasBruno LacarelleCharlotte StrettiElise KaspiAndrée Robaglia-SchluppCorinne Nicolino-BrunetCatherine TamaletNicolas LévyIsabelle Poizot-MartinPierre CauPatrice RollThe ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The present report focuses on lamin A processing, a pathway known to be altered in systemic genetic progeroid syndromes.35 HIV-1 infected patients being treated with first line antiretroviral therapy (ART, mean duration at inclusion: 2.7±1.3 years) containing boosted protease inhibitors (PI/r) (comprising lopinavir/ritonavir in 65% of patients) were recruited together with 49 seronegative age- and sex-matched control subjects (http://clinicaltrials.gov/, NCT01038999). In more than 88% of patients, the viral load was <40 copies/ml and the CD4+ cell count was >500/mm³. Prelamin A processing in peripheral blood mononuclear cells (PBMCs) from patients and controls was analysed by western blotting at inclusion. PBMCs from patients were also investigated at 12 and 24 months after enrolment in the study. PBMCs from healthy controls were also incubated with boosted lopinavir in culture medium containing various concentrations of proteins (4 to 80 g/L).Lamin A precursor was not observed in cohort patient PBMC regardless of the PI/r used, the dose and the plasma concentration. Prelamin A was detected in PBMC incubated in culture medium containing a low protein concentration (4 g/L) but not in plasma (60-80 g/L) or in medium supplemented with BSA (40 g/L), both of which contain a high protein concentration.Prelamin A processing abnormalities were not observed in PBMCs from patients under the PI/r first line regimen. Therefore, PI/r do not appear to contribute to lamin A-related aging in PBMCs. In cultured PBMCs from healthy donors, prelamin A processing abnormalities were only observed when the protein concentration in the culture medium was low, thus increasing the amount of PI available to enter cells. ClinicalTrials.gov NCT01038999 http://clinicaltrials.gov/ct2/show/NCT01038999.http://europepmc.org/articles/PMC3532351?pdf=render |
| spellingShingle | Sophie Perrin Jonathan Cremer Olivia Faucher Jacques Reynes Pierre Dellamonica Joëlle Micallef Caroline Solas Bruno Lacarelle Charlotte Stretti Elise Kaspi Andrée Robaglia-Schlupp Corinne Nicolino-Brunet Catherine Tamalet Nicolas Lévy Isabelle Poizot-Martin Pierre Cau Patrice Roll HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study. PLoS ONE |
| title | HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study. |
| title_full | HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study. |
| title_fullStr | HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study. |
| title_full_unstemmed | HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study. |
| title_short | HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study. |
| title_sort | hiv protease inhibitors do not cause the accumulation of prelamin a in pbmcs from patients receiving first line therapy the anrs ep45 aging study |
| url | http://europepmc.org/articles/PMC3532351?pdf=render |
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