Host-Immune Interactions in JC Virus Reactivation and Development of Progressive Multifocal Leukoencephalopathy (PML).

IF 5.2 3区医学 Q1 NEUROSCIENCES Journal of Neuroimmune Pharmacology Pub Date : 2019-12-01 Epub Date: 2019-08-27 DOI:10.1007/s11481-019-09877-8

Amir Khalili, Michael Craigie, Martina Donadoni, Ilker Kudret Sariyer

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Abstract

With the advent of immunomodulatory therapies and the HIV epidemic, the impact of JC Virus (JCV) on the public health system has grown significantly due to the increased incidence of Progressive Multifocal Leukoencephalopathy (PML). Currently, there are no pharmaceutical agents targeting JCV infection for the treatment and the prevention of viral reactivation leading to the development of PML. As JCV primarily reactivates in immunocompromised patients, it is proposed that the immune system (mainly the cellular-immunity component) plays a key role in the regulation of JCV to prevent productive infection and PML development. However, the exact mechanism of JCV immune regulation and reactivation is not well understood. Likewise, the impact of host factors on JCV regulation and reactivation is another understudied area. Here we discuss the current literature on host factor-mediated and immune factor-mediated regulation of JCV gene expression with the purpose of developing a model of the factors that are bypassed during JCV reactivation, and thus are potential targets for the development of therapeutic interventions to suppress PML initiation. Graphical Abstract.

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JC病毒活化和进行性多灶性白质脑病（PML）发展过程中的宿主免疫相互作用

随着免疫调节疗法的出现和艾滋病病毒（HIV）的流行，由于进行性多灶性白质脑病（Progressive Multifocal Leukoencephalopathy，PML）发病率的增加，JC 病毒（JCV）对公共卫生系统的影响也大大增加。目前，还没有针对 JCV 感染的药物来治疗和预防导致 PML 发生的病毒再活化。由于 JCV 主要在免疫力低下的患者中再活化，因此有人认为免疫系统（主要是细胞免疫成分）在调节 JCV 以防止产生性感染和 PML 的发展中起着关键作用。然而，JCV 免疫调节和再激活的确切机制尚不十分清楚。同样，宿主因素对 JCV 调节和再激活的影响也是另一个研究不足的领域。在此，我们讨论了目前有关宿主因子介导和免疫因子介导的 JCV 基因表达调控的文献，目的是建立一个模型，说明在 JCV 再激活过程中哪些因子被绕过，从而成为开发抑制 PML 启动的治疗干预措施的潜在靶点。图解摘要。

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来源期刊

Journal of Neuroimmune Pharmacology 医学-神经科学

CiteScore

13.60

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims of the Journal of Neuroimmune Pharmacology are to promote the dissemination, interest, and exchange of new and important discoveries for the pharmacology and immunology of the nervous system. The aims parallel that of the Society on NeuroImmune Pharmacology by increasing the fundamental understanding of neurologic and neuropsychiatric disorders affected by the immune system or vice versa and towards pharmacologic measures that lead, either to a better understanding of disease mechanisms, or by improving disease outcomes. The scope of JNIP includes all primary works and reviews into the etiology, prevention, and treatment of neuroimmune and nervous system diseases affected by disordered immunity. Original studies serving to define neuroimmune modulation of environmental or endogenous cues such as toxins and drugs of abuse, hormones, and cytokines are welcome. JNIP will serve as a reliable source of interdisciplinary information bridging the fields of pharmacology, immunology, and neuroscience.