Influence of the CCR-5/MIP-1 α Axis in the Pathogenesis of Rocio Virus Encephalitis in a Mouse Model
Influence of the CCR-5/MIP-1 α Axis in the Pathogenesis of Rocio Virus Encephalitis in a Mouse Model
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DOI：
10.4269/ajtmh.12-0591
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发表时间：
2013-11-01
影响因子：
3.3
通讯作者：
Figueiredo, Luiz T. M.
中科院分区：
文献类型：
--
作者：
Chavez, Juliana H.;Franca, Rafael F. O.;Figueiredo, Luiz T. M.
Rocio病毒（ROCV）在20世纪70年代在巴西引起了人类脑炎的爆发，其免疫发病机制仍然知之甚少。CC-趋化因子受体5（CCR 5）是一种与巨噬细胞炎性蛋白（MIP-1 α）结合的趋化因子受体。这两种分子都与感染期间的炎性细胞迁移有关。在这项研究中，我们证明了CCR 5和MIP-1 α在ROCV感染小鼠病毒性脑炎结局中的重要性。CCR 5和MIP-1 α基因敲除小鼠比野生型（WT）ROCV感染的动物存活更长时间。此外，基因敲除小鼠脑中的炎症减少。脑病毒载量的评估显示，野生型和CCR 5-/-小鼠在感染后5天检测到病毒，而MIP-1 α-/-小鼠在感染后7天的病毒载量较低。敲除小鼠也需要比野生型小鼠更高的致死剂量。CCR 5/MIP-1 α轴可能有助于感染细胞向脑的迁移，从而影响ROCV感染期间的发病机制。
Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 alpha). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 alpha, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 alpha knockout mice survived longer than wild-type (WT) ROCV-infected animals In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5-/- mice, while MIP-1 alpha-/- mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 alpha axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.