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安普那韦对慢性感染单核细胞/巨噬细胞中药物停药后 HIV-1 成熟、产生和感染性的影响。

Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages.

机构信息

Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Roma, Italy.

Clinical Virology Group, Institute of Biomedical Research of A Coruña (INIBIC)-University Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), 15001 A Coruña, Spain.

出版信息

Viruses. 2017 Sep 28;9(10):277. doi: 10.3390/v9100277.

DOI:10.3390/v9100277
PMID:28956865
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5691629/
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.

摘要

关于蛋白酶抑制剂(PI)在慢性感染的单核细胞衍生巨噬细胞(MDM)中的活性,以及在体外去除 PI 后病毒反弹的动力学方面,信息有限。为了填补这一空白,通过在药物给药后第 12 天和药物去除后第 7 天测量 p24 的产生,评估了不同浓度安普那韦(AMP)在慢性感染的 MDM 中的活性。临床相关浓度的 AMP(4 和 20 μM)从药物给药后第 2 天到第 12 天,大大降低了从慢性感染的 MDM 释放的 p24 量。AMP 去除(4 和 20 μM)后的病毒反弹动力学表明,尽管最初有所增加,但随着时间的推移,p24 的产生从未达到未处理的 MDM 观察到的水平,表明细胞内药物活性持续存在。与此一致的是,AMP 去除后,人类免疫缺陷病毒 1(HIV-1)感染性和细胞内 p24/p55 比值(反映病毒成熟)明显低于未处理的 MDM。总的来说,AMP 在阻断慢性感染的 MDM 中的 HIV-1 复制方面具有很高的疗效,即使在药物去除后也能持续存在。这突出了蛋白酶抑制剂在防止这种重要的 HIV-1 储存库建立方面的作用,从而减少了不同解剖部位的病毒传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/8cbb6c47b192/viruses-09-00277-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/e778522e1e5b/viruses-09-00277-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/785ddbdbc37c/viruses-09-00277-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/2fbad274bf1c/viruses-09-00277-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/1bc8ce966b8c/viruses-09-00277-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/8cbb6c47b192/viruses-09-00277-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/e778522e1e5b/viruses-09-00277-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/785ddbdbc37c/viruses-09-00277-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/2fbad274bf1c/viruses-09-00277-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/1bc8ce966b8c/viruses-09-00277-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1f8/5691629/8cbb6c47b192/viruses-09-00277-g005.jpg

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