Transcytosis of HIV-1 through vaginal epithelial cells is dependent on trafficking to the endocytic recycling pathway.
Transcytosis of HIV-1 through vaginal epithelial cells is dependent on trafficking to the endocytic recycling pathway.
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DOI：
10.1371/journal.pone.0096760
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Kinlock BL;Wang Y;Turner TM;Wang C;Liu B
虽然人们接受病毒可以通过内吞作用进入上皮细胞，但缺乏一种已建立的通过阴道上皮细胞运输感染性病毒粒子并将其从质膜释放的生物学机制，这导致了关于内吞作用是否仅仅是某些细胞培养系统的人工产物以及鳞状阴道上皮细胞是否与HIV-1传播相关的持续争议。在这项研究中，我们调查了细胞内运输途径，HIV-1利用转胞吞阴道上皮细胞。在细胞培养和transwell系统中，通过再循环内体抑制剂减少内体微管阻断了HIV-1的转胞吞作用。此外，我们证明，虽然热灭活的病毒被内吞有效的天然病毒，热灭活的病毒被专门贩运到溶酶体途径降解后的内吞作用。溶酶体蛋白酶特异性抑制剂阻断灭活病毒粒子的降解。免疫荧光分析不仅表明HIV-1在细胞内，而且天然与热灭活病毒与转铁蛋白的不同共定位模式提供了HIV-1使用再循环途径穿过阴道上皮细胞的确凿证据。总之，我们的发现证明了HIV-1在上皮细胞中利用的精确的细胞内运输途径，证实了HIV-1通过阴道上皮细胞的转胞吞作用是一种生物学现象，并揭示了天然与热灭活HIV-1的差异细胞内运输，进一步探索可以证明提供有价值的见解，可用于预防HIV-1的转胞吞作用/传播。1例穿过粘膜上皮。
While it is accepted that viruses can enter epithelial cells by endocytosis, the lack of an established biological mechanism for the trafficking of infectious virions through vaginal epithelial cells and their release from the plasma membrane has contributed to ongoing controversy about whether endocytosis is a mere artifact of some cell culture systems and whether squamous vaginal epithelial cells are even relevant as it pertains to HIV-1 transmission. In this study, we investigated the intracellular trafficking pathway that HIV-1 exploits to transcytose vaginal epithelial cells. The reduction of endosome tubulation by recycling endosome inhibitors blocked transcytosis of HIV-1 in a cell culture and transwell system. In addition, we demonstrate that although heat-inactivated virus was endocytosed as efficiently as native virus, heat-inactivated virus was trafficked exclusively to the lysosomal pathway for degradation following endocytosis. Lysosomal protease-specific inhibitors blocked the degradation of inactivated virions. Immunofluorescence analysis not only demonstrated that HIV-1 was inside the cells but the different colocalization pattern of native vs. heat inactivated virus with transferrin provided conclusive evidence that HIV-1 uses the recycling pathway to get across vaginal epithelial cells. Altogether, our findings demonstrate the precise intracellular trafficking pathway utilized by HIV-1 in epithelial cells, confirms that HIV-1 transcytosis through vaginal epithelial cells is a biological phenomenon and brings to light the differential intracellular trafficking of native vs heat-inactivated HIV-1 which with further exploration could prove to provide valuable insights that could be used in the prevention of transcytosis/transmission of HIV-1 across the mucosal epithelia.
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影响因子：
4.1
作者：
Drosten, C;M端ller-Kunert, E;Schmitz, H
通讯作者：
Schmitz, H
DOI：
10.1073/pnas.85.3.900
发表时间：
1988-02-01
影响因子：
11.1
作者：
ALOIA, RC;JENSEN, FC;GORDON, LM
通讯作者：
GORDON, LM
影响因子：
82.9
作者：
Bomsel, M
通讯作者：
Bomsel, M
影响因子：
32.4
作者：
Bobardt, MD;Saphire, ACS;Gallay, PA
通讯作者：
Gallay, PA
影响因子：
3.7
作者：
Fanibunda SE;Modi DN;Gokral JS;Bandivdekar AH
通讯作者：
Bandivdekar AH