Development of a mouse model for the study of Toscana virus pathogenesis
Development of a mouse model for the study of Toscana virus pathogenesis
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DOI：
10.1016/j.virol.2004.12.025
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发表时间：
2005-03-01
期刊：
影响因子：
3.7
通讯作者：
Miracco, C
中科院分区：
文献类型：
--
作者：
Cusi, MG;Savellini, GG;Miracco, C
托斯卡纳病毒（TOSV）最近被认为是一种由白蛉属媒介传播的新出现的病毒，是地中海国家急性神经系统疾病的原因。在我们的研究中，我们证明了成年Balb/c小鼠在脑内感染（ic.）或皮下（sc.）一种适应神经系统的病毒我们已经表明，通过在小鼠脑中进行TOSV的野生型人分离株的连续传代，发生了对高度毒力变体的选择，该高度毒力变体在ic的中枢神经系统（CNS）中有效复制。注射小鼠，造成急性脑炎和死亡。死后器官的免疫组织化学分析和TUNEL检测表明，TOSV复制高度限制于神经元，它诱导凋亡死亡，但是，在脾脏和淋巴结中也观察到病毒抗原阳性。在SC-在注射病毒的小鼠中，在脾脏和淋巴结中可检测到病毒，而只有很少的脑膜细胞和神经元受到影响，使得小鼠在感染后存活。在两种sc. -和IC。治疗的小鼠表明它们可能参与了感染的扩散。该动物模型可能有助于开发针对TOSV感染的预防措施。(C)2004爱思唯尔公司All rights reserved.
Toscana virus (TOSV) has recently been recognized as an emerging virus transmitted by phlebotomus vectors, responsible for acute neurological diseases in Mediterranean countries. In our study, we demonstrated that adult Balb/c mice were susceptible to TOSV when infected intracerebrally (ic.) or subcutaneously (sc.) with a neuroadapted strain of the virus. We have shown that by performing serial passages of a wild type human isolate of TOSV in mouse brains, selection occurs for a highly virulent variant which replicates efficiently in the central nervous system (CNS) of ic.-injected mice, causing acute encephalitis and death. Immunohistochemical analysis and TUNEL assay of post-mortem organs showed that TOSV replication was highly restricted to neurons in which it induced apoptotic death; however, virus antigen-positivity was also observed in the spleen and lymph nodes. In sc.-injected mice, virus was detectable in the spleen and lymph nodes, whereas only few meningeal cells and neurons were affected, allowing for the mouse survival the infection. The presence of TOSV in spleen and lymph node cells in both sc.- and ic.-treated mice suggests their possible involvement in the diffusion of the infection. This animal model may be helpful for the development of prophylactic measures against TOSV infections. (C) 2004 Elsevier Inc. All rights reserved.