Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, USA.
Viruses. 2023 Oct 18;15(10):2112. doi: 10.3390/v15102112.
JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining illness before antiretroviral therapy that has "reemerged" as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we discuss the evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model provides insights into the pathogenesis of JCPyV CNS disease.
JC 多瘤病毒（JCPyV）是一种人类特异性多瘤病毒，在免疫功能正常的个体的多个外周器官中建立无声的终身感染，主要是泌尿系统的器官。然而，在免疫功能低下的情况下，JCPyV 可以渗透到中枢神经系统（CNS），在那里它引起几种发病率和死亡率很高的脑病。JCPyV 诱导的进行性多灶性白质脑病（PML）是一种破坏性的脱髓鞘脑疾病，在抗逆转录病毒治疗之前是艾滋病的定义性疾病，并且已经“重新出现”为免疫调节和化学治疗药物的并发症。目前尚无有效的抗多瘤病毒治疗方法。免疫抑制状态如何为 JCPyV 在泌尿系统中的再次出现奠定基础，病毒如何逃避预先存在的抗病毒抗体而成为病毒血症，以及它如何进入中枢神经系统，这些都不完全清楚。解决这些问题需要一种可处理的 JCPyV 中枢神经系统感染动物模型。尽管没有任何动物模型可以复制任何人类疾病的所有方面，但小鼠多瘤病毒（MuPyV）在小鼠中和 JCPyV 在人类中具有外周和中枢神经系统感染以及抗病毒免疫的关键特征。在这篇综述中，我们讨论了表明 JCPyV 如何从外周迁移到中枢神经系统、先天和适应性免疫对多瘤病毒感染的反应以及 MuPyV-小鼠模型如何提供对 JCPyV 中枢神经系统疾病发病机制的见解的证据。
