HIV gp120 binds to mannose receptor on vaginal epithelial cells and induces production of matrix metalloproteinases.
HIV gp120 binds to mannose receptor on vaginal epithelial cells and induces production of matrix metalloproteinases.
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DOI：
10.1371/journal.pone.0028014
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bandivdekar AH
中科院分区：
文献类型：
--
作者：
Fanibunda SE;Modi DN;Gokral JS;Bandivdekar AH
在女性艾滋病毒的性传播过程中，病毒突破阴道的多层CD 4阴性复层鳞状上皮屏障，感染上皮下CD 4阳性免疫细胞。然而，艾滋病毒进入上皮下区的机制迄今尚不清楚。我们以前曾报道过人甘露糖受体（hMR）作为一种CD 4非依赖性受体在人类精子上的HIV传播中发挥作用。本研究旨在探讨hMR在阴道上皮细胞中的表达、hMR与HIV gp 120的结合能力、亲和常数以及hMR对HIV gp 120下游基质金属蛋白酶（MMP）的诱导作用。本研究使用人阴道上皮细胞和永生化阴道上皮细胞系Vk 2/E6 E7。hMR mRNA和蛋白在阴道上皮细胞和细胞系中表达，分子量为155 kDa。HIV gp 120以高亲和力与阴道蛋白结合（阴道细胞的Kd=1.2±0.2 nM，细胞系的Kd = 1.4±0.2 nM），hMR拮抗剂甘露聚糖剂量依赖性地抑制这种结合。 通过免疫荧光，HIV gp 120结合和hMR在上皮细胞中表现出相同的定位模式。HIV gp 120与免疫纯化的hMR结合，对阴道细胞和Vk 2/E6 E7细胞系的亲和常数分别为2.9± 0.4nM和3.2± 0.6nM。HIV gp 120诱导MMP-9 mRNA表达和活性的增加，通过酶谱法，这可以被抑制的抗hMR抗体。由阴道上皮细胞表达的hMR对HIV gp 120具有高亲和力，并且这种结合诱导MMPs的产生。我们建议，诱导MMPs响应HIV gp 120可能会导致阴道上皮和基底膜中的紧密连接蛋白和细胞外基质蛋白的降解，导致上皮屏障的减弱，从而促进HIV通过阴道上皮的运输。
During sexual transmission of HIV in women, the virus breaches the multi-layered CD4 negative stratified squamous epithelial barrier of the vagina, to infect the sub-epithelial CD4 positive immune cells. However the mechanisms by which HIV gains entry into the sub-epithelial zone is hitherto unknown. We have previously reported human mannose receptor (hMR) as a CD4 independent receptor playing a role in HIV transmission on human spermatozoa. The current study was undertaken to investigate the expression of hMR in vaginal epithelial cells, its HIV gp120 binding potential, affinity constants and the induction of matrix metalloproteinases (MMPs) downstream of HIV gp120 binding to hMR. Human vaginal epithelial cells and the immortalized vaginal epithelial cell line Vk2/E6E7 were used in this study. hMR mRNA and protein were expressed in vaginal epithelial cells and cell line, with a molecular weight of 155 kDa. HIV gp120 bound to vaginal proteins with high affinity, (Kd = 1.2±0.2 nM for vaginal cells, 1.4±0.2 nM for cell line) and the hMR antagonist mannan dose dependently inhibited this binding. Both HIV gp120 binding and hMR exhibited identical patterns of localization in the epithelial cells by immunofluorescence. HIV gp120 bound to immunopurified hMR and affinity constants were 2.9±0.4 nM and 3.2±0.6 nM for vaginal cells and Vk2/E6E7 cell line respectively. HIV gp120 induced an increase in MMP-9 mRNA expression and activity by zymography, which could be inhibited by an anti-hMR antibody. hMR expressed by vaginal epithelial cells has high affinity for HIV gp120 and this binding induces production of MMPs. We propose that the induction of MMPs in response to HIV gp120 may lead to degradation of tight junction proteins and the extracellular matrix proteins in the vaginal epithelium and basement membrane, leading to weakening of the epithelial barrier; thereby facilitating transport of HIV across the vaginal epithelium.
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影响因子：
32.4
作者：
Hladik, Florian;Sakchalathorn, Polachai;Ballweber, Lamar;Lentz, Gretchen;Fialkow, Michael;Eschenbach, David;McElrath, M. Juliana
通讯作者：
McElrath, M. Juliana
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通讯作者：
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4.8
作者：
Lai, Joey;Bernhard, Oliver K.;Cunningham, Anthony L.
通讯作者：
Cunningham, Anthony L.
影响因子：
2.8
作者：
Gazi, Umut;Martinez-Pomares, Luisa
通讯作者：
Martinez-Pomares, Luisa
影响因子：
3.7
作者：
Cummins NW;Klicpera A;Sainski AM;Bren GD;Khosla S;Westendorf JJ;Badley AD
通讯作者：
Badley AD