Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice.
Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice.
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DOI：
10.1186/1742-2094-8-23
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发表时间：
2011-03-09
影响因子：
9.3
通讯作者：
Teixeira AL
中科院分区：
文献类型：
--
作者：
Amaral DC;Rachid MA;Vilela MC;Campos RD;Ferreira GP;Rodrigues DH;Lacerda-Queiroz N;Miranda AS;Costa VV;Campos MA;Kroon EG;Teixeira MM;Teixeira AL
登革热是人类最重要的虫媒病毒病之一，可引起严重的全身性疾病。虽然登革病毒(DENV)被认为是一种非嗜神经性病毒，但最近登革热感染与包括脑炎在内的一系列神经综合征有关。在这项工作中，我们研究了非适应登革病毒3型(DENV-3)基因I感染C57BL/6小鼠的行为变化和炎症参数。在感染后第3天和第6天(P.I.)，我们用活体显微镜观察白细胞在脑微血管中的转运，并用ELISA法检测趋化因子和细胞因子的变化。此外，我们还测定了髓过氧化物酶活性和免疫细胞数量，并对脑组织中的病毒进行了组织病理学分析和免疫组化染色。所有动物都出现了脑炎症状，并在第8天P.I.死亡。运动行为、肌张力和力量参数在P.I.第7天下降。在感染第3天和第6天，我们观察到感染小鼠脑微血管中白细胞滚动和黏附增加。在感染之后，干扰素-γ、肿瘤坏死因子-α、CCL2、CCL5、CXCL1和CXCL2显著增加。组织学分析显示有脑膜脑炎和反应性胶质细胞增生症。中性粒细胞、CD_4~+和CD_8~+T细胞在感染动物的脑组织中明显增多，尤以感染后第6天最为明显。脑内可见抗NS-3免疫反应阳性的细胞。未适应的DENV-3脑内感染可导致小鼠死亡前的脑炎和行为改变。
Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted dengue virus 3 (DENV-3) genotype I. C57BL/6 mice received 4 × 103 PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the virus in brain tissue. All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN-γ, TNF-α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4+ and CD8+ T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain. Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice.
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影响因子：
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作者：
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