轴突
生物
小胶质细胞
多发性硬化
髓鞘
转基因
实验性自身免疫性脑脊髓炎
细胞生物学
神经退行性变
表型
内生
病毒学
免疫学
神经科学
基因
中枢神经系统
医学
遗传学
病理
炎症
生物化学
疾病
作者
Joel Gruchot,Isabel Lewen,Michael Dietrich,Laura Reiche,Mustafa Sindi,Christina Hecker,Felisa Herrero,Benjamin Charvet,Ulrike Weber‐Stadlbauer,Hans‐Peter Hartung,Philipp Albrecht,Hervé Perron,Urs Meyer,Patrick Küry
标识
DOI:10.1073/pnas.2308187120
摘要
The human endogenous retrovirus type W (HERV-W) has been identified and repeatedly confirmed as human-specific pathogenic entity affecting many cell types in multiple sclerosis (MS). Our recent contributions revealed the encoded envelope (ENV) protein to disturb myelin repair by interfering with oligodendroglial precursor differentiation and by polarizing microglial cells toward an axon-damage phenotype. Indirect proof of ENV's antiregenerative and degenerative activities has been gathered recently in clinical trials using a neutralizing anti-ENV therapeutic antibody. Yet direct proof of its mode of action can only be presented here based on transgenic ENV expression in mice. Upon demyelination, we observed myelin repair deficits, neurotoxic microglia and astroglia, and increased axon degeneration. Experimental autoimmune encephalomyelitis activity progressed faster in mutant mice equally accompanied by activated glial cells. This study therefore provides direct evidence on HERV-W ENV's contribution to the overall negative impact of this activated viral entity in MS.
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