Basolateral localization of fiber receptors limits adenovirus infection from the apical surface of airway epithelia
Basolateral localization of fiber receptors limits adenovirus infection from the apical surface of airway epithelia
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DOI：
10.1074/jbc.274.15.10219
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发表时间：
1999-04-09
影响因子：
4.8
通讯作者：
Zabner, J
中科院分区：
文献类型：
--
作者：
Walters, RW;Grunst, T;Zabner, J
最近鉴定出腺病毒纤维蛋白的两种受体，即柯萨奇 B 型和腺病毒 2 型和 5 型受体 (CAR)，以及主要组织相容性复合体 (MHC) I 类 alpha-2 结构域，从而可以研究腺病毒感染的分子基础。早期的工作表明，人气道上皮细胞对腺病毒感染有抵抗力，因此，我们在分化良好、有纤毛的人气道上皮细胞体外模型中检测了CAR和MHC I类的表达和定位。我们发现气道上皮表达 CAR 和 MHC I 类。然而，这两种受体都不存在于顶膜中；相反，两者都被极化到基底外侧膜。这些发现解释了顶端表面对腺病毒感染的相对抵抗力。相比之下，当病毒应用于基底外侧表面时，由于腺病毒纤维与其受体的相互作用，基因转移效率更高。此外，当紧密连接的完整性短暂破坏时，顶部应用的腺病毒可以进入基底外侧表面并增强基因转移。这些数据表明，有效感染所需的受体在顶端表面上不存在，而允许进入纤维受体所在的基底外侧空间的干预措施可以提高基因转移效率。
Recent identification of two receptors for the adenovirus fiber protein, coxsackie B and adenovirus type 2 and 5 receptor (CAR), and the major histocompatibility complex (MHC) Class I alpha-2 domain allows the molecular basis of adenoviral infection to be investigated. Earlier work has shown that human airway epithelia are resistant to infection by adenovirus, Therefore, we examined the expression and localization of CAR and MHC Class I in an in vitro model of well differentiated, ciliated human airway epithelia. We found that airway epithelia express CAR and MHC Class I. However, neither receptor was present in the apical membrane; instead, both were polarized to the basolateral membrane. These findings explain the relative resistance to adenovirus infection from the apical surface. In contrast, when the virus was applied to the basolateral surface, gene transfer was much more efficient because of an interaction of adenovirus fiber with its receptors, In addition, when the integrity of the tight junctions was transiently disrupted, apically applied adenovirus gained access to the basolateral surface and enhanced gene transfer. These data suggest that the receptors required for efficient infection are not available on the apical surface, and interventions that allow access to the basolateral space where fiber receptors are located increase gene transfer efficiency.