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粗制宫颈黏液塞在游离细胞和细胞间传播情况下对 HIV-1 感染的屏障功能。

The barrier functions of crude cervical mucus plugs against HIV-1 infection in the context of cell-free and cell-to-cell transmission.

机构信息

University of Cape Town, Department of Surgery, Groote Schuur Hospital, Observatory, South Africa.

TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Institute of Experimental Virology, Hannover.

出版信息

AIDS. 2021 Nov 1;35(13):2105-2117. doi: 10.1097/QAD.0000000000003003.

DOI:10.1097/QAD.0000000000003003
PMID:34155151
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8505157/
Abstract

OBJECTIVE

The cervical mucus plugs are enriched with proteins of known immunological functions. We aimed to characterize the anti-HIV-1 activity of the cervical mucus plugs against a panel of different HIV-1 strains in the contexts of cell-free and cell-associated virus.

DESIGN

A cohort of consenting HIV-1-negative and HIV-1-positive pregnant women in labour was recruited from Mthatha General Hospital in the Eastern Cape province of South Africa, from whom the cervical mucus plugs were collected in 6 M guanidinium chloride with protease inhibitors and transported to our laboratories at -80 °C.

METHODS

Samples were centrifuged to remove insoluble material and dialysed before freeze--drying and subjecting them to the cell viability assays. The antiviral activities of the samples were studied using luminometric reporter assays and flow cytometry. Time-of-addition and BlaM-Vpr virus-cell fusion assays were used to pin-point the antiviral mechanisms of the cervical mucus plugs, before proteomic profiling using liquid chromatography-tandem mass spectrometry.

RESULTS

The proteinaceous fraction of the cervical mucus plugs exhibited anti-HIV-1 activity with inter-individual variations and some degree of specificity among different HIV-1 strains. Cell-associated HIV-1 was less susceptible to inhibition by the potent samples whenever compared with the cell-free HIV-1. The samples with high antiviral potency exhibited a distinct proteomic profile when compared with the less potent samples.

CONCLUSION

The crude cervical mucus plugs exhibit anti-HIV-1 activity, which is defined by a specific proteomic profile.

摘要

目的

宫颈黏液栓富含具有已知免疫功能的蛋白质。我们旨在研究宫颈黏液栓在细胞外和细胞相关病毒的情况下,针对不同 HIV-1 株的抗 HIV-1 活性。

设计

从南非东开普省姆塔塔总医院招募了一批同意的 HIV-1 阴性和 HIV-1 阳性孕妇,从她们那里收集了用 6M 盐酸胍和蛋白酶抑制剂处理的宫颈黏液栓,并在-80°C 下运送到我们的实验室。

方法

将样品离心以去除不溶性物质,并在冷冻干燥前进行透析,然后进行细胞活力测定。使用发光报告测定法和流式细胞术研究样品的抗病毒活性。使用时间添加和 BlaM-Vpr 病毒-细胞融合测定法来确定宫颈黏液栓的抗病毒机制,然后使用液相色谱-串联质谱法进行蛋白质组学分析。

结果

宫颈黏液栓的蛋白部分表现出抗 HIV-1 活性,个体间存在差异,对不同 HIV-1 株具有一定程度的特异性。与细胞外 HIV-1 相比,细胞相关 HIV-1 对强样本的抑制作用较弱。与弱效样本相比,具有高抗病毒效力的样本表现出明显不同的蛋白质组学特征。

结论

粗制宫颈黏液栓表现出抗 HIV-1 活性,其特征是特定的蛋白质组学特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/51222c50a471/aids-35-2105-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/03838f6f3c74/aids-35-2105-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/4c0fe434b628/aids-35-2105-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/b4939898aa91/aids-35-2105-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/46ae9ebb9188/aids-35-2105-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/51222c50a471/aids-35-2105-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/03838f6f3c74/aids-35-2105-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/4c0fe434b628/aids-35-2105-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/b4939898aa91/aids-35-2105-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/46ae9ebb9188/aids-35-2105-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb0c/8505157/51222c50a471/aids-35-2105-g005.jpg

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