MAVS mediates a protective immune response in the brain to Rift Valley fever virus.
MAVS mediates a protective immune response in the brain to Rift Valley fever virus.
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MAVS介导了大脑中的保护性免疫反应，以促进裂谷发烧病毒。
DOI：
10.1371/journal.ppat.1010231
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发表时间：
2022-05
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
裂谷热病毒（RVFV）是一种高致病性蚊媒病毒，能够引起人类和牲畜的肝炎、脑炎、失明、出血性综合征和死亡。RVFV气溶胶感染后，脑是病毒复制和组织损伤的主要部位，但该器官的发病机制尚未充分研究。在这里，我们研究了RVFV感染小鼠脑中的免疫应答。在对感染的反应中，小胶质细胞启动了抗病毒免疫基因的稳健转录上调，以及依赖于线粒体抗病毒信号蛋白（MAVS）和独立于Toll样受体3和7的激活标志物和细胞因子分泌水平的增加。在体内，Mavs-/-小鼠表现出对RVFV的易感性增强，如通过增加的脑病毒负荷和更高的死亡率所确定的。单细胞RNA序列分析确定了Mavs-/-小鼠小胶质细胞内I型干扰素和干扰素应答基因表达的缺陷，以及淋巴细胞浸润失调。这项研究的结果为了解RVFV感染在大脑中控制的精确分子机制迈出了关键一步，并将有助于开发有效预防脑炎的疫苗和抗病毒疗法。裂谷热病毒在人类和牲畜中引起严重疾病，在某些情况下可能致命。人们对使用裂谷热病毒作为生物武器感到关切，因为它可以通过空气传播，而且没有疫苗或抗病毒治疗。病毒的空气传播会导致大脑严重炎症，但人们对这个器官中针对病毒的免疫反应知之甚少。在这里，我们研究了裂谷热病毒鼻内感染后大脑中的免疫反应。我们确定了小胶质细胞，大脑的常驻免疫细胞，对裂谷热病毒感染发起了强烈的反应，并确定了一个关键的免疫途径，这对小胶质细胞对感染的反应能力至关重要。当这种免疫途径失去功能时，小鼠对大脑中的感染反应失调。这项研究提供了深入了解免疫反应如何控制裂谷热病毒感染的大脑。
Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogenesis in this organ has been understudied. Here, we investigated the immune response in the brain of RVFV infected mice. In response to infection, microglia initiated robust transcriptional upregulation of antiviral immune genes, as well as increased levels of activation markers and cytokine secretion that is dependent on mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. In vivo, Mavs-/- mice displayed enhanced susceptibility to RVFV as determined by increased brain viral burden and higher mortality. Single-cell RNA sequence analysis identified defects in type I interferon and interferon responsive gene expression within microglia in Mavs-/- mice, as well as dysregulated lymphocyte infiltration. The results of this study provide a crucial step towards understanding the precise molecular mechanisms by which RVFV infection is controlled in the brain and will help inform the development of vaccines and antiviral therapies that are effective in preventing encephalitis. Rift Valley fever virus causes severe disease in humans and livestock and in some cases can be fatal. There is concern about the use of Rift Valley fever virus as a bioweapon since it can be transmitted through the air, and there are no vaccines or antiviral treatments. Airborne transmission of the virus causes severe inflammation of the brain, yet little is known about the immune response against the virus in this organ. Here, we investigated the immune response in the brain to Rift Valley fever virus following intranasal infection. We determined that microglia, the resident immune cells of the brain, initiate a robust response to Rift Valley fever virus infection and identified a key immune pathway that is critical for the ability of microglia to respond to infection. When this immune pathway is rendered non-functional, mice have a dysregulated response to infection in the brain. This study provides insight into how the immune response can control Rift Valley fever virus infection of the brain.
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影响因子：
30.5
作者：
Goldmann T;Wieghofer P;Jordão MJ;Prutek F;Hagemeyer N;Frenzel K;Amann L;Staszewski O;Kierdorf K;Krueger M;Locatelli G;Hochgerner H;Zeiser R;Epelman S;Geissmann F;Priller J;Rossi FM;Bechmann I;Kerschensteiner M;Linnarsson S;Jung S;Prinz M
通讯作者：
Prinz M
影响因子：
5.4
作者：
Harmon B;Bird SW;Schudel BR;Hatch AV;Rasley A;Negrete OA
通讯作者：
Negrete OA
DOI：
10.4269/ajtmh.2010.09-0293
发表时间：
2010-08-01
影响因子：
3.3
作者：
Anyangu, Amwayi S.;Gould, L. Hannah;Breiman, Robert F.
通讯作者：
Breiman, Robert F.
影响因子：
14.8
作者：
Brewer, Gregory J.;Torricelli, John R.
通讯作者：
Torricelli, John R.
影响因子：
32.4
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
通讯作者：
Stevens, Beth