Viral infections of the central nervous system: pathogenesis to therapeutics.
Viral infections of the central nervous system: pathogenesis to therapeutics.
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中枢神经系统的病毒感染：发病机制到治疗。
DOI：
10.1007/s11481-010-9231-x
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Jacobson,Steven
中科院分区：
文献类型：
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作者：
Soldan,SamanthaS;Jacobson,Steven
中枢神经系统的病毒感染与许多使人衰弱的疾病有关，包括慢性神经退行性和神经炎性疾病、神经精神疾病、急性脑炎和中枢神经系统恶性肿瘤。尽管这些多种疾病的影响是毁灭性的，在某些情况下会导致死亡，但我们可以利用的有效疫苗和治疗药物来预防和治疗病毒介导的中枢神经系统疾病的数量惊人地有限。因此，我们必须更好地了解这些疾病所涉及的神经炎症和神经退行性变的常见机制，以便开发更有效的治疗方法。在本期《神经免疫药理学杂志》中，我们汇集了来自神经病毒学领域的领军人物的不同寻常的稿件，包括全面综述和主要研究文章。本文中包含的手稿集中于由不同家族的病毒引起或与之相关的各种中枢神经系统疾病，并强调了临床和基础研究结果支持的病毒诱导的神经发病机制。最终，阐明病毒介导的神经毒性的途径和这些不同条件下的神经炎症过程将导致开发与病毒感染相关的中枢神经系统异质性疾病的治疗策略。HIV相关性神经认知障碍(HAND)的神经发病机制复杂，但很明显，先天和获得性免疫因素都参与了疾病的进展。Shah博士和他的同事的贡献为适应性免疫系统和先天免疫系统在HIV发病机制中的作用提供了极好的综述。先天免疫因素很重要，不仅在调节炎症方面，而且在直接抑制艾滋病毒复制方面(Shah等人。2010)。此外，还详细讨论了炎症介质，特别是细胞因子和趋化因子在HIV-1疾病中的作用(Shah等人。2010)。巨噬细胞和星形胶质细胞都参与了感染者中枢神经系统的炎症和神经元病理，尽管大部分损伤是由促炎细胞因子和趋化因子介导的，但现在人们认识到，趋化因子也可能具有神经保护作用，起到神经递质和神经调节剂的作用。因此，需要更好地了解免疫系统的先天和适应性手臂对中枢神经系统慢性病毒疾病的贡献，并最终可能被利用来获得治疗收益。艾滋病毒-1感染的抗逆转录病毒疗法(ART)的使用改善了病毒学控制，并延长了艾滋病毒感染者的预期寿命。然而，尽管有这些有效的抗病毒药物可用，HAND的流行率已经增加，这突显了需要
Viral infections of the CNS have been implicated in many debilitating illnesses including chronic neurodegenerative and neuroinflammatory disorders, neuropsychiatric conditions, acute encephalitis, and CNS malignancies. Although the effects of these manifold diseases are devastating, leading to death in some instances, the armamentarium of effective vaccines and therapeutics at our disposal to prevent and treat virus-mediated disorders of the CNS is astoundingly limited. It is, therefore, critical that we achieve a better understanding of the common mechanisms of neuroinflammation and neurodegeneration involved in these disorders so that more effective therapeutics can be developed. In this special issue of the Journal of Neuroimmune Pharmacology, we have assembled an extraordinary collection of contributions, including both comprehensive reviews and primary research articles, from leaders in the field of neurovirology. The manuscripts contained herein focus on a variety of CNS diseases caused by or associated with viruses from disparate families and highlight virusinduced mechanisms of neuropathogenesis supported by both clinical and basic research findings. Ultimately, the elucidation of pathways of virus-mediated neurotoxicity and the neuroinflammatory processes underlying these various conditions will lead to the development of treatment strategies for heterogenous disorders of the CNS associated with viral infection.The neuropathogenesis of HIV-associated neurocognitive disorders (HAND) is complex, but it is clear that both innate and adaptive immune factors are involved in disease progression. The contribution from Dr. Shah and colleagues provides an excellent review of the role of the adaptive and innate immune systems in HIV pathogenesis. Innate immune factors are important, not only in mediating inflammation, but also in directly inhibiting HIV replication (Shah et al. 2010). In addition, the contributions of inflammatory mediators, cytokines and chemokines in particular, to HIV-1 disease are discussed at length (Shah et al. 2010). Both macrophages and astrocytes contribute to inflammation and neuronal pathology in the CNS of infected individuals and, although much of the damage is mediated by pro-inflammatory cytokines and chemokines, it is now appreciated that chemokines may also have a neuroprotective role and act as neurotransmitters and neuromodulators. Therefore, a better understanding of the contributions of both the innate and adaptive arms of the immune system to chronic virus diseases of the CNS is needed and may ultimately be harnessed for therapeutic gain. The use of antiretroviral therapy (ART) for HIV-1 infection has improved virological control and increased the life expectancy of HIV-infected individuals. However, despite the availability of these potent antivirals, the prevalence of HAND has increased, underscoring the need