A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system.
A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system.
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DOI：
10.1016/j.isci.2021.102678
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发表时间：
2021-06-25
期刊：
影响因子：
5.8
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Yang D;Lin T;Li C;Harrison AG;Geng T;Wang P
巨噬细胞清道夫受体1（macrophage scavenger receptor 1，MSR 1）在宿主防御细菌感染、M2巨噬细胞极化和脂质稳态中起重要作用。然而，其在病毒发病机制中的生理功能仍然不清楚。在此，我们报告，MSR 1促进水泡性口炎病毒（VSV）感染中枢神经系统。与同窝出生的Msr 1 +/−小鼠和野生型小鼠相比，Msr 1-缺陷（Msr 1-/−）小鼠在致死性VSV感染后的发病率、死亡率和脊髓中的病毒载量降低，沿着正常的病毒血症和先天免疫应答。MSR 1表达在脊髓中最显著上调，脊髓是VSV的主要靶点。从机制上讲，MSR 1通过其胞外结构域与VSV表面糖蛋白相互作用，并以低密度脂蛋白受体依赖性方式促进其进入细胞。总之，我们的研究结果表明，MSR 1作为VSV细胞进入的辅助因子，并促进其感染优先在脊髓。MSR 1在小鼠中促进VSV发病MSR 1在中枢神经系统中高度上调并促进VSV感染MSR 1以LDLR家族依赖性方式促进VSV进入细胞MSR 1通过其细胞外结构域与VSV糖蛋白G相互作用分子生理学;神经科学;病毒学;细胞生物学
Macrophage scavenger receptor 1 (MSR1) plays an important role in host defense to bacterial infections, M2 macrophage polarization, and lipid homeostasis. However, its physiological function in viral pathogenesis remains poorly defined. Herein, we report that MSR1 facilitates vesicular stomatitis virus (VSV) infection in the central nervous system. Msr1-deficient (Msr1−/−) mice presented reduced morbidity, mortality, and viral loads in the spinal cord following lethal VSV infection, along with normal viremia and innate immune responses, compared to Msr1+/− littermates and wild-type mice. Msr1 expression was most significantly upregulated in the spinal cord, the predominant target of VSV. Mechanistically, through its extracellular domains, MSR1 interacted with VSV surface glycoprotein and facilitated its cellular entry in a low-density lipoprotein receptor-dependent manner. In conclusion, our results demonstrate that MSR1 serves as a cofactor for VSV cellular entry and facilitates its infection preferentially in the spinal cord. MSR1 contributes to VSV pathogenesis in mice MSR1 is highly upregulated and facilitates VSV infection in the central nervous system MSR1 facilitates cellular entry of VSV in an LDLR family-dependent manner MSR1 interacts with VSV glycoprotein G via its extracellular domains Molecular physiology; Neuroscience; Virology; Cell biology
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