Rocchi Angela, Sariyer Ilker K, Berger Joseph R
Department of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA.
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Convention Avenue, Philadelphia, PA, 19104, USA.
J Neurovirol. 2023 Oct;29(5):524-537. doi: 10.1007/s13365-023-01164-w. Epub 2023 Sep 2.
Since its definition 65 years ago, progressive multifocal leukoencephalopathy (PML) has continued to devastate a growing population of immunosuppressed patients despite major advances in our understanding of the causative JC virus (JCV). Unless contained by the immune system, JCV lyses host oligodendrocytes collateral to its life cycle, leading to demyelination, neurodegeneration, and death. Novel treatments have stagnated in the absence of an animal model while current antiviral agents fail to address the now ubiquitous polyomavirus. In this review, we highlight the established pathogenesis by which JCV infection progresses to PML, highlighting major challenges that must be overcome to eliminate the underlying virus and, therefore, the debilitating disease.
自65年前被定义以来，尽管我们对致病性JC病毒（JCV）的认识取得了重大进展，但进行性多灶性白质脑病（PML）仍在继续摧毁越来越多的免疫抑制患者群体。除非被免疫系统控制，JCV在其生命周期中会裂解宿主少突胶质细胞，导致脱髓鞘、神经退行性变和死亡。在缺乏动物模型的情况下，新型治疗方法停滞不前，而目前的抗病毒药物无法应对现在无处不在的多瘤病毒。在这篇综述中，我们强调了JCV感染发展为PML的既定发病机制，突出了消除潜在病毒从而消除这种使人衰弱的疾病必须克服的主要挑战。
