Complement activation is required for induction of a protective antibody response against West Nile virus infection
Complement activation is required for induction of a protective antibody response against West Nile virus infection
复制标题
DOI：
10.1128/jvi.79.12.7466-7477.2005
复制
发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Diamond, MS
中科院分区：
文献类型：
--
作者：
Mehlhop, E;Whitby, K;Diamond, MS
西尼罗河病毒（WNV）感染可导致中枢神经系统（CNS）严重感染，老年人和免疫功能低下者的发病率和死亡率较高。小鼠实验已经开始确定先天免疫和适应性免疫反应如何限制感染。在这里，我们证明了补体系统，先天免疫的一个主要组成部分，在体外主要以抗体依赖的方式控制西尼罗河病毒感染，通过中和溶液中的病毒颗粒和裂解西尼罗河病毒感染的细胞。更决定性的是，基因上缺乏补体或补体受体1 （CR1）和CR2第三组分的小鼠，中枢神经系统病毒负荷增加，在低剂量西尼罗病毒感染下易受致命感染。c3缺陷和CR1和cr2缺陷小鼠在感染后的体液反应也有显著缺陷，特异性抗西尼罗河病毒免疫球蛋白M （IgM）和IgG水平显著降低。总的来说，这些结果表明补体控制西尼罗河病毒感染，部分是通过其诱导保护性抗体反应的能力。
Infection with West Nile virus (WNV) causes a severe infection of the central nervous system (CNS) with higher levels of morbidity and mortality in the elderly and the immunocompromised. Experiments with mice have begun to define how the innate and adaptive immune responses function to limit infection. Here, we demonstrate that the complement system, a major component of innate immunity, controls WNV infection in vitro primarily in an antibody-dependent manner by neutralizing virus particles in solution and lysing WNV-infected cells. More decisively, mice that genetically lack the third component of complement or complement receptor 1 (CR1) and CR2 developed increased CNS virus burdens and were vulnerable to lethal infection at a low dose of WNV. Both C3-deficient and CR1- and CR2-deficient mice also had significant deficits in their humoral responses after infection with markedly reduced levels of specific anti-WNV immunoglobulin M (IgM) and IgG. Overall, these results suggest that complement controls WNV infection, in part through its ability to induce a protective antibody response.