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Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages
A paucity of information is available on the activity of protease inhibitors (PI) in chronically-infected monocyte-derived macrophages (MDM) and on the kinetics of viral-rebound after PI removal in vitro. To fill this gap, the activity of different concentrations of amprenavir (AMP) was evaluated in...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691629/ https://www.ncbi.nlm.nih.gov/pubmed/28956865 http://dx.doi.org/10.3390/v9100277 |
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author | Borrajo, Ana Ranazzi, Alessandro Pollicita, Michela Bruno, Rosalinda Modesti, Andrea Alteri, Claudia Perno, Carlo Federico Svicher, Valentina Aquaro, Stefano |
author_facet | Borrajo, Ana Ranazzi, Alessandro Pollicita, Michela Bruno, Rosalinda Modesti, Andrea Alteri, Claudia Perno, Carlo Federico Svicher, Valentina Aquaro, Stefano |
author_sort | Borrajo, Ana |
collection | PubMed |
description | A paucity of information is available on the activity of protease inhibitors (PI) in chronically-infected monocyte-derived macrophages (MDM) and on the kinetics of viral-rebound after PI removal in vitro. To fill this gap, the activity of different concentrations of amprenavir (AMP) was evaluated in chronically-infected MDM by measuring p24-production every day up to 12 days after drug administration and up to seven days after drug removal. Clinically-relevant concentrations of AMP (4 and 20 μM) drastically decreased p24 amount released from chronically-infected MDM from Day 2 up to Day 12 after drug administration. The kinetics of viral-rebound after AMP-removal (4 and 20 μM) showed that, despite an initial increase, p24-production over time never reached the level observed for untreated-MDM, suggesting a persistent intracellular drug activity. In line with this, after AMP-removal, human immunodeficiency virus 1 (HIV-1) infectivity and intracellular the p24/p55 ratio (reflecting virion-maturation) were remarkably lower than observed for untreated MDM. Overall, AMP shows high efficacy in blocking HIV-1 replication in chronically-infected MDM, persisting even after drug-removal. This highlights the role of protease inhibitors in preventing the establishment of this important HIV-1 reservoir, thus reducing viral-dissemination in different anatomical compartments. |
format | Online Article Text |
id | pubmed-5691629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-56916292017-11-22 Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages Borrajo, Ana Ranazzi, Alessandro Pollicita, Michela Bruno, Rosalinda Modesti, Andrea Alteri, Claudia Perno, Carlo Federico Svicher, Valentina Aquaro, Stefano Viruses Article A paucity of information is available on the activity of protease inhibitors (PI) in chronically-infected monocyte-derived macrophages (MDM) and on the kinetics of viral-rebound after PI removal in vitro. To fill this gap, the activity of different concentrations of amprenavir (AMP) was evaluated in chronically-infected MDM by measuring p24-production every day up to 12 days after drug administration and up to seven days after drug removal. Clinically-relevant concentrations of AMP (4 and 20 μM) drastically decreased p24 amount released from chronically-infected MDM from Day 2 up to Day 12 after drug administration. The kinetics of viral-rebound after AMP-removal (4 and 20 μM) showed that, despite an initial increase, p24-production over time never reached the level observed for untreated-MDM, suggesting a persistent intracellular drug activity. In line with this, after AMP-removal, human immunodeficiency virus 1 (HIV-1) infectivity and intracellular the p24/p55 ratio (reflecting virion-maturation) were remarkably lower than observed for untreated MDM. Overall, AMP shows high efficacy in blocking HIV-1 replication in chronically-infected MDM, persisting even after drug-removal. This highlights the role of protease inhibitors in preventing the establishment of this important HIV-1 reservoir, thus reducing viral-dissemination in different anatomical compartments. MDPI 2017-09-28 /pmc/articles/PMC5691629/ /pubmed/28956865 http://dx.doi.org/10.3390/v9100277 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Borrajo, Ana Ranazzi, Alessandro Pollicita, Michela Bruno, Rosalinda Modesti, Andrea Alteri, Claudia Perno, Carlo Federico Svicher, Valentina Aquaro, Stefano Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages |
title | Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages |
title_full | Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages |
title_fullStr | Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages |
title_full_unstemmed | Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages |
title_short | Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages |
title_sort | effects of amprenavir on hiv-1 maturation, production and infectivity following drug withdrawal in chronically-infected monocytes/macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691629/ https://www.ncbi.nlm.nih.gov/pubmed/28956865 http://dx.doi.org/10.3390/v9100277 |
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