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肠道病毒感染的受体与宿主因素:对癌症治疗的启示

Receptors and Host Factors for Enterovirus Infection: Implications for Cancer Therapy.

作者信息

Alekseeva Olga N, Hoa Le T, Vorobyev Pavel O, Kochetkov Dmitriy V, Gumennaya Yana D, Naberezhnaya Elizaveta R, Chuvashov Denis O, Ivanov Alexander V, Chumakov Peter M, Lipatova Anastasia V

机构信息

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.

Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

出版信息

Cancers (Basel). 2024 Sep 12;16(18):3139. doi: 10.3390/cancers16183139.

Abstract

Enteroviruses, with their diverse clinical manifestations ranging from mild or asymptomatic infections to severe diseases such as poliomyelitis and viral myocarditis, present a public health threat. However, they can also be used as oncolytic agents. This review shows the intricate relationship between enteroviruses and host cell factors. Enteroviruses utilize specific receptors and coreceptors for cell entry that are critical for infection and subsequent viral replication. These receptors, many of which are glycoproteins, facilitate virus binding, capsid destabilization, and internalization into cells, and their expression defines virus tropism towards various types of cells. Since enteroviruses can exploit different receptors, they have high oncolytic potential for personalized cancer therapy, as exemplified by the antitumor activity of certain enterovirus strains including the bioselected non-pathogenic Echovirus type 7/Rigvir, approved for melanoma treatment. Dissecting the roles of individual receptors in the entry of enteroviruses can provide valuable insights into their potential in cancer therapy. This review discusses the application of gene-targeting techniques such as CRISPR/Cas9 technology to investigate the impact of the loss of a particular receptor on the attachment of the virus and its subsequent internalization. It also summarizes the data on their expression in various types of cancer. By understanding how enteroviruses interact with specific cellular receptors, researchers can develop more effective regimens of treatment, offering hope for more targeted and efficient therapeutic strategies.

摘要

肠道病毒临床表现多样,从轻度或无症状感染到脊髓灰质炎和病毒性心肌炎等严重疾病,对公共卫生构成威胁。然而,它们也可用作溶瘤剂。本综述展示了肠道病毒与宿主细胞因子之间的复杂关系。肠道病毒利用特定的受体和共受体进入细胞,这些对于感染及随后的病毒复制至关重要。这些受体许多是糖蛋白,有助于病毒结合、衣壳不稳定以及内化进入细胞,它们的表达决定了病毒对各种类型细胞的嗜性。由于肠道病毒可利用不同受体,它们在个性化癌症治疗方面具有很高的溶瘤潜力,某些肠道病毒株(如经生物筛选的非致病性7型艾柯病毒/Rigvir,已获批用于治疗黑色素瘤)的抗肿瘤活性就是例证。剖析单个受体在肠道病毒进入过程中的作用,可为其在癌症治疗中的潜力提供有价值的见解。本综述讨论了基因靶向技术(如CRISPR/Cas9技术)在研究特定受体缺失对病毒附着及其随后内化的影响方面的应用。它还总结了这些受体在各种类型癌症中的表达数据。通过了解肠道病毒如何与特定细胞受体相互作用,研究人员可以制定更有效的治疗方案,为更有针对性和高效的治疗策略带来希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/11430599/0944df18edbb/cancers-16-03139-g001.jpg

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