Landers Maeran Chung, Dugger Natalie, Quadros Marlene, Hoffman Paul M, Gaulton Glen N
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Virology. 2004 Mar 30;321(1):57-64. doi: 10.1016/j.virol.2003.12.002.
Exposure of newborn BALB/c mice to murine leukemia virus (MLV) TR1.3 induces fusion of brain capillary endothelial cells (BCEC), loss of cerebral vessel integrity, hemorrhagic stroke, and death. Although TR1.3 infects endothelial cells in multiple organs, syncytia are only observed in BCEC. To determine if viral and cellular factors are responsible for selective syncytia formation, capillary endothelial cells (CEC) from multiple organs were assayed in vitro for MLV infection and cell fusion. Following incubation with virus, all CEC were infected to an equal extent as determined by expression of MLV envelope and infectious virus production; however, MLV-induced syncytia were only observed in TR1.3-infected BCEC cultures. These in vitro results mirror the in vivo pattern of TR1.3 MLV infection and neuropathology, and definitively show that selective fusion and pathology of BCEC by MLV is determined by properties unique to BCEC as contrasted to other endothelial cell types.
将新生BALB/c小鼠暴露于鼠白血病病毒(MLV)TR1.3会诱导脑毛细血管内皮细胞(BCEC)融合、脑血管完整性丧失、出血性中风和死亡。尽管TR1.3感染多个器官的内皮细胞,但仅在BCEC中观察到多核巨细胞。为了确定病毒和细胞因子是否导致选择性多核巨细胞形成,对来自多个器官的毛细血管内皮细胞(CEC)进行体外MLV感染和细胞融合检测。与病毒孵育后,通过MLV包膜表达和传染性病毒产生确定所有CEC受到同等程度的感染;然而,仅在TR1.3感染的BCEC培养物中观察到MLV诱导的多核巨细胞。这些体外结果反映了TR1.3 MLV感染和神经病理学的体内模式,并明确表明MLV对BCEC的选择性融合和病理学是由BCEC特有的特性决定的,这与其他内皮细胞类型形成对比。