Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan; Department of Microbiology, Faculty of Veterinary Medicine, Okayama University of Science, Ehime 794-8555, Japan.
Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Trends Microbiol. 2019 Feb;27(2):164-175. doi: 10.1016/j.tim.2018.08.010. Epub 2018 Sep 13.
Measles virus (MeV) may persist in the brain, causing fatal neurodegenerative diseases, subacute sclerosing panencephalitis, and measles inclusion-body encephalitis. However, the mechanism of MeV propagation in the brain remains unexplained because human neurons affected by the diseases do not express the known receptors for MeV. Recent studies have revealed that certain changes in the ectodomain of the MeV fusion (F) protein play a key role in MeV spread in the brain. These changes destabilize the prefusion form of the F protein and render it hyperfusogenic, which in turn allows the virus to propagate in neurons. Based on crystal structures of the F protein, effective fusion inhibitors could be developed to treat these diseases.
麻疹病毒(MeV)可能在大脑中持续存在,导致致命的神经退行性疾病,如亚急性硬化性全脑炎和麻疹包涵体脑炎。然而,MeV 在大脑中传播的机制仍不清楚,因为受这些疾病影响的人类神经元不表达已知的 MeV 受体。最近的研究表明,MeV 融合(F)蛋白的外域中的某些变化在 MeV 在大脑中的传播中起着关键作用。这些变化会使 F 蛋白的预融合形式失稳,并使其具有超融合性,从而使病毒能够在神经元中传播。基于 F 蛋白的晶体结构,可以开发有效的融合抑制剂来治疗这些疾病。