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.

Effects of amprenavir on HIV-1 maturation, production and infectivity following drug withdrawal in chronically-infected monocytes/macrophages / A. Borrajo, A. Ranazzi, M. Pollicita, R. Bruno, A. Modesti, C. Alteri, C. Perno, V. Svicher, S. Aquaro. - In: VIRUSES. - ISSN 1999-4915. - 9:10(2017 Sep 28), pp. 277.1-277.12. [10.3390/v9100277]

Effects of amprenavir on HIV-1 maturation, production and infectivity following drug withdrawal in chronically-infected monocytes/macrophages

C. Alteri;C. Perno;
2017

Abstract

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.
English
Amprenavir; Human immunodeficiency virus; Monocytes/macrophages; Protease inhibitors; Infectious Diseases; Virology
Settore MED/07 - Microbiologia e Microbiologia Clinica
Articolo
Esperti anonimi
Pubblicazione scientifica
28-set-2017
MDPI
9
10
277
1
12
12
Pubblicato
Periodico con rilevanza internazionale
Aderisco
info:eu-repo/semantics/article
Effects of amprenavir on HIV-1 maturation, production and infectivity following drug withdrawal in chronically-infected monocytes/macrophages / A. Borrajo, A. Ranazzi, M. Pollicita, R. Bruno, A. Modesti, C. Alteri, C. Perno, V. Svicher, S. Aquaro. - In: VIRUSES. - ISSN 1999-4915. - 9:10(2017 Sep 28), pp. 277.1-277.12. [10.3390/v9100277]
open
Prodotti della ricerca::01 - Articolo su periodico
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262
Article (author)
Periodico con Impact Factor
A. Borrajo, A. Ranazzi, M. Pollicita, R. Bruno, A. Modesti, C. Alteri, C. Perno, V. Svicher, S. Aquaro
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/623157
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