当前位置: X-MOL 学术ACS Chem. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Identification of Interferon Receptor IFNAR2 As a Novel HCV Entry Factor by Using Chemical Probes.
ACS Chemical Biology ( IF 4 ) Pub Date : 2020-02-03 , DOI: 10.1021/acschembio.9b00912
Jie Qing 1, 2 , Ming Wu 2 , Rui Luo 3 , Jizheng Chen 4 , Lin Cao 5 , Debin Zeng 6 , Luqing Shang 6 , Junxiu Nong 3 , Qinkai Wu 7 , Bi-Sen Ding 8 , Xinwen Chen 4 , Zihe Rao 3 , Lei Liu 2 , Zhiyong Lou 3
Affiliation  

Upon sensing pathogen-associated patterns and secreting interferons (IFNs) into the environment, host cells perceive extracellular type I IFNs by the IFNα/β receptors IFNAR1 and IFNAR2 to stimulate downstream innate immune signaling cascades. Through the use of chemical probes, we demonstrated that IFNAR2 facilitates hepatitis C virus (HCV) entry. Silencing of IFNAR2 significantly attenuated HCV proliferation. IFNAR2 binds infectious HCV virions through a direct interaction of its D2 domain with the C-terminal end of apolipoprotein E (apoE) on the viral envelope and facilitates virus entry into host cells. The antibody against the IFNAR2 D2 domain attenuates IFNAR2-apoE interaction and impairs HCV infection. The recombinant IFNAR2 protein and the chemical probe potently inhibit major HCV genotypes in various human liver cells in vitro. Moreover, the impact of a chemical probe on HCV genotype 2a is also documented in immune-compromised humanized transgenic mice. Our results not only expand the understanding of the biology of HCV entry and the virus-host relationship but also reveal a new target for the development of anti-HCV entry inhibitors.

中文翻译:

通过使用化学探针鉴定干扰素受体IFNAR2作为新型HCV进入因子。

在检测到病原体相关模式并向环境中分泌干扰素(IFN)后,宿主细胞通过IFNα/β受体IFNAR1和IFNAR2感知细胞外I型IFN,以刺激下游先天免疫信号级联反应。通过使用化学探针,我们证明了IFNAR2促进丙型肝炎病毒(HCV)进入。沉默IFNAR2会大大减弱HCV的增殖。IFNAR2通过其D2域与病毒包膜上载脂蛋白E(apoE)的C末端直接相互作用而与感染性HCV病毒粒子结合,并促进病毒进入宿主细胞。抗IFNAR2 D2域的抗体会减弱IFNAR2-apoE的相互作用并削弱HCV感染。重组IFNAR2蛋白和化学探针可有效抑制体外各种人肝细胞中主要的HCV基因型。此外,在免疫受损的人源化转基因小鼠中也记录了化学探针对HCV基因型2a的影响。我们的结果不仅扩大了对HCV进入生物学和病毒-宿主关系的理解,而且揭示了开发抗HCV进入抑制剂的新目标。
更新日期:2020-01-23
down
wechat
bug