登革热包膜蛋白作为诱导小鼠出血和内皮细胞死亡的细胞毒性因素
Te-Sheng Lien1, Der-Shan Sun1, Wen-Sheng Wu2,3
1Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 970, Taiwan.
International journal of molecular sciences
|October 16, 2024
概括
登革热病毒包膜蛋白域III (EIII) 触发内皮细胞死亡,导致登革热出血性发烧 (DHF). 针对EIII,反应性氧物种和caspase-3亡提供了潜在的DHF疗法.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 病变的发生和发病.
背景情况:
- 登革热病毒 (DENV) 感染导致登革热出血热 (DHF),其特点是内皮损伤和血管泄漏.
- 目前尚无针对DHF的特定抗病毒治疗方法,并未完全了解导致内皮损伤的病毒因素.
研究的目的:
- 研究DENV包膜蛋白域III (EIII) 在诱导内皮细胞亡中的作用.
- 探索细胞死亡途径作为潜在的治疗点的DHF.
主要方法:
- 在体外研究中,使用人体内皮细胞 (HMEC-1) 接受了复合EIII (rEIII) 和DENV治疗.
- 在体内小鼠模型模仿DHF与连续的rEIII和抗血小板免疫球蛋白注射.
- 评估caspase-3活性,细胞亡和DHF类症状 (血小板缩,出血,炎症,高凝血).
主要成果:
- 复合EIII和DENV诱导的caspase-3介导的内皮细胞死亡在体外,减少了氏丁硫酸盐B (CSB),N-乙半氨酸 (NAC) 和z-DEVD-FMK.
- 在小鼠中,双重rEIII和免疫球蛋白治疗诱导了在出血部位的caspase-3依赖性内皮细胞亡.
- z-DEVD-FMK治疗降低了DHF症状;CSB和NAC缓解了出血.
结论:
- DENV EIII有助于内皮细胞亡和DHF病变的发生.
- 准EIII,活性氧物种和卡斯帕-3介导的亡为DHF提供了一个有前途的治疗策略.
相关概念视频
01:25Arboviral Encephalitis
Arboviral encephalitis refers to brain inflammation caused by arthropod-borne viruses, particularly those transmitted through mosquito vectors. Among these, West Nile virus (WNV), a member of the Flaviviridae family, is a significant public health concern. WNV is an enveloped, positive-sense, single-stranded RNA virus. Human infection typically begins when an infected mosquito introduces the virus into the dermis during feeding. The primary transmission cycle involves birds as amplifying hosts...
01:18Yellow Fever
Yellow fever is a viral hemorrhagic disease caused by the yellow fever virus (YFV), a member of the Flaviviridae family. It is transmitted primarily by Aedes and Haemagogus mosquitoes in tropical and subtropical regions of Africa and South America. After transmission through a mosquito bite, the virus initially replicates in skin-resident immune cells such as dendritic cells and macrophages. These cells then migrate to the lymph nodes, where viral replication increases, eventually leading to...