Abstract

Cyclophilin A (CypA), a key member of the immunophilin family, is the most abundantly expressed isozyme of the 18 known human cyclophilins. Besides acting as an intracellular receptor for cyclosporine A, CypA plays a vital role in microorganismal infections, cardiovascular diseases, liver diseases, kidney diseases, neurodegeneration, cancer, rheumatoid arthritis, periodontitis, sepsis, asthma, and aging. This review focuses on the pivotal roles of CypA in the infection of etiological agents, which manifests mainly in promoting or inhibiting viral replication based on the host cell type and viral species. CypA can interact with viral proteins and thus regulate the replication cycle of the virus. CypA is involved in pathogenic bacterial infections by regulating the formation of host actin skeleton or membrane translocation of bacterial toxins, or mediated the adhesion of Mycoplasma genitalium during the infection processes by acting as a cellular receptor of M. genitalium. CypA also plays a critical role in infection or the life cycle of certain parasites or host immune regulation. Moreover, we summarized the current understanding of CypA inhibitors acting as host-targeting antiviral agents, thus opening an avenue for the treatment of multiple viral infections due to their broad antiviral effects and ability to effectively prevent drug resistance. Therefore, the antiviral effect of CypA has the potential to promote CypA inhibitors as host-targeting drugs to CypA-involved etiological agent infections and human diseases.

Key points

• CypA is involved in the replication and infection of several viruses, pathogenic bacteria, mycoplasma, and parasites.

• CypA inhibitors are in a strong position to inhibit the infection of viruses, bacterial, and mycoplasma.

中文翻译：

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亲环素 A：病原体感染的关键因素

摘要

亲环蛋白 A (CypA) 是亲免蛋白家族的关键成员，是 18 种已知人类亲环蛋白中表达最丰富的同工酶。除了作为环孢素 A 的细胞内受体外，CypA 在微生物感染、心血管疾病、肝脏疾病、肾脏疾病、神经退行性变、癌症、类风湿性关节炎、牙周炎、败血症、哮喘和衰老中也起着至关重要的作用。本综述重点关注 CypA 在病原体感染中的关键作用，主要表现为根据宿主细胞类型和病毒种类促进或抑制病毒复制。CypA 可以与病毒蛋白相互作用，从而调节病毒的复制周期。CypA 通过调节宿主肌动蛋白骨架的形成或细菌毒素的膜易位参与病原性细菌感染，生殖支原体在感染过程中充当生殖支原体的细胞受体。CypA 在感染或某些寄生虫的生命周期或宿主免疫调节中也起着关键作用。此外，我们总结了目前对 CypA 抑制剂作为宿主靶向抗病毒剂的认识，从而为治疗多种病毒感染开辟了道路，因为它们具有广泛的抗病毒作用和有效预防耐药性的能力。因此，CypA 的抗病毒作用具有促进 CypA 抑制剂作为宿主靶向药物治疗 CypA 相关病原体感染和人类疾病的潜力。

关键点

• CypA 参与多种病毒、病原菌、支原体和寄生虫的复制和感染。

• CypA 抑制剂在抑制病毒、细菌和支原体感染方面具有很强的作用。