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脊髓灰质炎病毒侵入与发病机制中的病毒-受体相互作用

Virus-receptor interaction in poliovirus entry and pathogenesis.

作者信息

Racaniello V R

机构信息

Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York.

出版信息

Harvey Lect. 1991;87:1-16.

PMID:1670545
Abstract

Knowledge of the three-dimensional structure of poliovirus has provided insight into many aspects of poliovirus infection. However, the structure alone cannot answer questions about how the virus interacts with the receptor to lead to release of the genome into the cell. Genetic and biochemical analysis of virus mutants are required to understand these steps in infection. The availability of cDNA clones of the poliovirus genome and PVR enables the isolation of virus and PVR mutants that can be used to study early events in infection. The results of these studies, coupled with the resolution of the three-dimensional structure of PVR, and perhaps of a PVR-poliovirus complex, should provide a detailed picture of virus binding, alteration, and uncoating. Viral receptors do not exist solely for the benefit of viruses, but serve a particular function in the cell. The study of virus receptors, therefore, bridges the disciplines of virology and cell biology. Identification of viral receptors may reveal previously unknown cell proteins whose functions can be studied, or might enhance our knowledge of a known protein. As a member of the Ig superfamily of proteins, PVR is likely to have a role in cell adhesion and/or cell-cell communication. It will, therefore, be important to identify a PVR ligand or coreceptor. The study of the expression of PVR and its ligand will provide a basis for understanding the normal function of this protein. Determination of the function of MPH will be facilitated by the analysis of mice containing a targeted disruption of the MPH gene. It is likely that knowledge of the cell function of MPH can also provide information on the interaction of poliovirus with host cells. It has been suggested that virus binding to cell receptors may lead to activation of cell events that lead to disease (69). While there is no evidence that poliovirus affects cells in this way, studying the interaction of MPH with its ligand might provide clues about cell processes that may be activated by poliovirus infection.

摘要

脊髓灰质炎病毒三维结构的知识为深入了解脊髓灰质炎病毒感染的许多方面提供了线索。然而,仅靠结构本身无法回答病毒如何与受体相互作用从而导致基因组释放到细胞内的问题。需要对病毒突变体进行遗传和生化分析,以了解感染过程中的这些步骤。脊髓灰质炎病毒基因组和脊髓灰质炎病毒受体(PVR)的cDNA克隆的可得性,使得能够分离出可用于研究感染早期事件的病毒和PVR突变体。这些研究结果,再加上PVR三维结构以及可能的PVR - 脊髓灰质炎病毒复合物结构的解析,应该能够提供病毒结合、改变和解衣壳过程的详细图景。病毒受体并非仅仅为病毒而存在,而是在细胞中发挥特定功能。因此,对病毒受体的研究跨越了病毒学和细胞生物学两个学科。病毒受体的鉴定可能会揭示此前未知的细胞蛋白,从而可以对其功能进行研究,或者可能会增进我们对已知蛋白的了解。作为免疫球蛋白超家族蛋白的一员,PVR可能在细胞黏附和/或细胞间通讯中发挥作用。因此,鉴定PVR配体或共受体将非常重要。对PVR及其配体表达的研究将为理解该蛋白的正常功能提供基础。对含有MPH基因靶向破坏的小鼠进行分析,将有助于确定MPH的功能。了解MPH的细胞功能也可能为脊髓灰质炎病毒与宿主细胞的相互作用提供信息。有人提出病毒与细胞受体的结合可能会导致引发疾病的细胞事件的激活(69)。虽然没有证据表明脊髓灰质炎病毒以这种方式影响细胞,但研究MPH与其配体的相互作用可能会提供有关可能被脊髓灰质炎病毒感染激活的细胞过程的线索。

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