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首页> 外文期刊>Reviews in medical virology >Innate immune response during herpes simplex virus encephalitis and development of immunomodulatory strategies
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Innate immune response during herpes simplex virus encephalitis and development of immunomodulatory strategies

机译：单纯疱疹病毒性脑炎的先天免疫应答及免疫调节策略的发展

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摘要

Herpes simplex viruses are large double-stranded DNA viruses. These viruses have the ability to establish a lifelong latency in sensory ganglia and to invade and replicate in the CNS. Apart from relatively benign mucosal infections, HSV is responsible for severe illnesses including HSV encephalitis (HSE). HSE is the most common cause of sporadic, potentially fatal viral encephalitis in Western countries. If left untreated, the mortality rate associated with HSE is approximately 70%. Despite antiviral therapy, the mortality is still higher than 30%, and almost 60% of surviving individuals develop neurological sequelae. It is suggested that direct virus-related and indirect immune-mediated mechanisms contribute to the damages occurring in the CNS during HSE. In this manuscript, we describe the innate immune response to HSV, the development of HSE in mice knock-out for proteins of the innate immune system as well as inherited deficiencies in key components of the signaling pathways involved in the production of type I interferon that could predispose individuals to develop HSE. Finally, we review several immunomodulatory strategies aimed at modulating the innate immune response at a critical time after infection that were evaluated in mouse models and could be combined with antiviral therapy to improve the prognosis of HSE. In conclusion, the cerebral innate immune response that develops during HSE is a "double-edged sword" as it is critical to control viral replication in the brain early after infection, but, if left uncontrolled, may also result in an exaggerated inflammatory response that could be detrimental to the host. Copyright (C) 2015 John Wiley & Sons, Ltd.
机译：单纯疱疹病毒是大型双链DNA病毒。这些病毒具有在感觉神经节中建立终生潜伏期并在CNS中入侵和复制的能力。除相对良性的粘膜感染外，HSV还引起包括HSV脑炎（HSE）在内的严重疾病。 HSE是西方国家散发性，潜在致命性病毒性脑炎的最常见原因。如果不加以治疗，与HSE相关的死亡率约为70％。尽管进行了抗病毒治疗，死亡率仍然高于30％，并且幸存的个体中有近60％会出现神经系统后遗症。提示直接的病毒相关和间接的免疫介导的机制是造成HSE期间中枢神经系统发生损害的原因。在本手稿中，我们描述了对HSV的先天免疫应答，小鼠中HSE的发育，先天免疫系统蛋白的敲除以及涉及生产I型干扰素的信号通路关键成分的遗传缺陷。可能使个人容易发展HSE。最后，我们综述了几种旨在调节感染后关键时刻的先天免疫应答的免疫调节策略，这些策略已在小鼠模型中进行了评估，可与抗病毒治疗相结合以改善HSE的预后。总之，HSE期间发生的大脑先天免疫反应是一把“双刃剑”，因为在感染后早期控制大脑中的病毒复制至关重要，但如果不加以控制，也可能导致过度的炎症反应，可能对主机有害。版权所有（C）2015 John Wiley＆Sons，Ltd.

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