Katherine J D A Excoffon, Jonathan R Bowers, Priyanka Sharma
Understanding the biology of cell surface proteins is important particularly when they are utilized as viral receptors for viral entry. By manipulating the expression of cell surface receptors that have been coopted by viruses, the susceptibility of an individual to virus-induced disease or, alternatively, the effectiveness of viral-based gene therapy can be modified. The most commonly studied vector for gene therapy is adenovirus. The majority of adenovirus types utilize the coxsackievirus and adenovirus receptor (CAR) as a primary receptor to enter cells. Species B adenovirus do not interact with CAR, but instead interact with the cell surface proteins desmoglein-2 (DSG-2) and cluster of differentiation 46 (CD46). These cell surface proteins exhibit varying degrees of alternative mRNA splicing, creating an estimated 20 distinct protein isoforms. It is likely that alternative splice forms have allowed these proteins to optimize their effectiveness in a plethora of niches, including roles as cell adhesion proteins and regulators of the innate immune system. Interestingly, there are soluble isoforms of these viral receptors, which lack the transmembrane domain. These soluble isoforms can potentially bind to the surface of a virus in the extracellular compartment, blocking the ability of the virus to bind to the host cell, reducing viral infectivity. Finally, the diversity of viral receptor isoforms appears to facilitate an assortment of interactions between viral receptor proteins and cytosolic proteins, leading to differential sorting in polarized cells. Using adenoviral receptors as a model system, the purpose of this review is to highlight the role that isoform-specific protein localization plays in the entry of pathogenic viruses from the apical surface of polarized epithelial cells.
了解细胞表面蛋白的生物学特性非常重要，尤其是当这些蛋白被用作病毒受体用于病毒侵入时。通过操纵被病毒利用的细胞表面受体的表达，可以改变个体对病毒引起的疾病的易感性，或者改变基于病毒的基因疗法的有效性。最常研究的基因治疗载体是腺病毒。大多数腺病毒类型利用柯萨奇病毒和腺病毒受体（CAR）作为主要受体进入细胞。B 型腺病毒不与 CAR 相互作用，而是与细胞表面蛋白脱模谷蛋白-2（DSG-2）和分化簇 46（CD46）相互作用。这些细胞表面蛋白表现出不同程度的 mRNA 替代剪接，产生了大约 20 种不同的蛋白质异构体。替代剪接形式很可能使这些蛋白质能够优化其在多种环境中的作用，包括作为细胞粘附蛋白和先天性免疫系统的调节因子。有趣的是，这些病毒受体存在缺乏跨膜结构域的可溶性异构体。这些可溶性异构体有可能在细胞外与病毒表面结合，阻止病毒与宿主细胞结合，从而降低病毒的感染力。最后，病毒受体异构体的多样性似乎有助于病毒受体蛋白与细胞膜蛋白之间的各种相互作用，从而导致极化细胞中的不同分选。本综述以腺病毒受体为模型系统，旨在强调同工酶特异性蛋白定位在致病病毒从极化上皮细胞顶端表面进入过程中所起的作用。
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