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West Nile Virus spread and differential chemokine response in the central nervous system of mice: Role in pathogenic mechanisms of encephalitis.
Transboundary and Emerging Diseases ( IF 4.3 ) Pub Date : 2019-11-15 , DOI: 10.1111/tbed.13401
Beatriz Vidaña 1 , Nicholas Johnson 2 , Anthony R Fooks 2 , Pedro J Sánchez-Cordón 1 , Daniel J Hicks 1 , Alejandro Nuñez 1
Affiliation  

West Nile virus (WNV) is a zoonotic mosquito-borne flavivirus able to cause severe neurological disease in humans, horses and various avian species. The more severe pathological changes of neurotropic WNV infection are caused by virus neuroinvasion and/or the immunological response in the central nervous system (CNS). The extent in which inflammatory cell trafficking orchestrated by chemokines is involved in the pathogenesis of CNS lesions has not been entirely elucidated. To understand the sequence of pro-inflammatory chemokine induction during WNV encephalitis, a murine intranasal inoculation model was used. The relationship between lesional patterns in the mice CNS, the viral antigen distribution and the expression of pro-inflammatory chemokine (CCL2, CCL5 and CXCL10) were evaluated. Viral antigen was first observed in olfactory tract and pyriform cortex neurons, suggesting a retrograde neuronal infection from the olfactory nerve. A spatio-temporal association between WNV antigen and perivascular cuffs development was observed. Chemokine immunostaining was widely distributed in the brain from early stages. CCL2 immunolabelling was localised in neurons, astrocytes, microglia and endothelial cells as well as mononuclear leucocytes within perivascular cuffs. In contrast, CCL5 and CXCL10 immunostaining were mainly observed in astroglia and neurons, respectively. A strong correlation was demonstrated between the presence of perivascular cuffs and CCL2 and CCL5 expression in most brain areas, while CXCL10 was only associated with inflammatory lesions in few specific regions. Importantly, a strong correlation between WNV and CCL5 distribution was observed. However, no correlation was observed between CXCL10 and viral antigen. Neurons were confirmed as the main target cells of WNV, as well as one of the sources of CCL2, CCL5 and CXCL10. This study shows the sequence and comparative distribution pattern between histological lesions, WNV antigen and chemokine expression over the infection process. Furthermore, it identifies potential targets for immune intervention to suppress damaging chemokine responses.

中文翻译:

西尼罗河病毒在小鼠中枢神经系统中的扩散和趋化因子反应的差异:在脑炎的致病机制中的作用。

西尼罗河病毒(WNV)是一种人畜共患的蚊媒黄病毒,能够在人,马和各种鸟类中引起严重的神经系统疾病。嗜神经性WNV感染的更为严重的病理变化是由病毒神经入侵和/或中枢神经系统(CNS)的免疫反应引起的。由趋化因子精心策划的炎症细胞运输参与中枢神经系统病变发病机制的程度尚未完全阐明。为了了解在WNV脑炎期间促炎性趋化因子诱导的顺序,使用了小鼠鼻内接种模型。评估了小鼠中枢神经系统病变模式,病毒抗原分布和促炎性趋化因子(CCL2,CCL5和CXCL10)表达之间的关系。病毒抗原首先在嗅觉和梨状皮层神经元中观察到,提示嗅觉神经发生逆行性神经元感染。观察到WNV抗原和血管周套发展之间的时空关联。从早期起,趋化因子免疫染色就广泛分布在大脑中。CCL2免疫标记定位在血管周套内的神经元,星形胶质细胞,小胶质细胞和内皮细胞以及单核白细胞中。相反,CCL5和CXCL10免疫染色主要在星形胶质细胞和神经元中观察到。在大多数大脑区域,血管周套的存在与CCL2和CCL5表达之间存在强烈的相关性,而CXCL10仅与少数特定区域的炎性病变相关。重要的,观察到WNV和CCL5分布之间有很强的相关性。但是,在CXCL10和病毒抗原之间没有发现相关性。神经元被确认为WNV的主要靶细胞,也是CCL2,CCL5和CXCL10的来源之一。这项研究显示了感染过程中组织学病变,WNV抗原和趋化因子表达之间的序列和比较分布模式。此外,它确定了免疫干预的潜在靶点,以抑制破坏性的趋化因子反应。WNV抗原和趋化因子在感染过程中的表达。此外,它确定了免疫干预的潜在靶点,以抑制破坏性的趋化因子反应。WNV抗原和趋化因子在感染过程中的表达。此外,它确定了免疫干预的潜在靶点,以抑制破坏性的趋化因子反应。
更新日期:2019-11-15
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