BAAV transcytosis requires an interaction with beta-1-4 linked- glucosamine and gp96.

BAAV transcytosis requires an interaction with beta-1-4 linked- glucosamine and gp96.
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DOI:
10.1371/journal.pone.0009336
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发表时间:
2010-03-09
期刊:
影响因子:
3.7
通讯作者:
Chiorini JA
Chiorini JA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Di Pasquale G;Kaludov N;Agbandje-McKenna M;Chiorini JA

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细胞表面碳水化合物在病毒进入和细胞内运输中发挥重要作用。牛腺相关病毒 (BAAV) 使用质膜神经节苷脂进行转导和感染。此外,独立于感染途径,BAAV 还能够利用依赖于细胞表面碳水化合物存在的转胞吞途径穿过屏障上皮和内皮细胞。因此,为了更好地确定 BAAV 感染或转胞吞作用所需的碳水化合物相互作用,用 HA 标记的 BAAV 颗粒探测由天然和合成碳水化合物组成的聚糖微阵列。这鉴定出壳三糖(β-1-4 连接的 N-乙酰氨基葡萄糖的三聚体)与 BAAV 具有相互作用。竞争实验表明,BAAV 与这种碳水化合物的相互作用对于感染来说不是必需的,但在转胞吞途径中却很重要。据报道,gp96 上有 β-1-4 连接的 N-乙酰氨基葡萄糖修饰,gp96 是一种参与细菌和毒素转胞吞作用的糖蛋白。值得注意的是,分别使用抗 gp96 抗体和可溶形式的 gp96 进行的免疫沉淀和竞争实验表明,这种糖蛋白也可以与 BAAV 相互作用,作为其转胞吞作用的受体。
Cell surface carbohydrates play an important role in virus entry and intracellular trafficking. Bovine Adeno-Associated Virus (BAAV) uses plasma membrane gangliosides for transduction and infection. In addition, independent of the infectious pathway, BAAV also has the ability to pass through barrier epithelia and endothelia using a transcytosis pathway dependent upon the presence of cell surface carbohydrates. Thus, in order to better define the carbohydrate interactions that are necessary for BAAV infection or transcytosis, a glycan microarray composed of both natural and synthetic carbohydrates was probed with HA-tagged BAAV particles. This identified chitotriose, a trimer of β-1-4-linked N-acetyl glucosamine, as having an interaction with BAAV. Competition experiments showed that the BAAV interaction with this carbohydrate is not necessary for infection but is instead important in the transcytosis pathway. The β-1-4-linked N-acetyl glucosamine modification has been reported on gp96, a glycoprotein involved in the transcytosis of bacteria and toxins. Significantly, immunoprecipitation and competition experiments with an anti-gp96 antibody and a soluble form of gp96, respectively, showed this glycoprotein can also interact with BAAV to serve as a receptor for its transcytosis.
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