Craig L E, Nealen M L, Strandberg J D, Zink M C
Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Virology. 1997 Nov 24;238(2):316-26. doi: 10.1006/viro.1997.8830.
Blood-brain barrier dysfunction has been postulated to be important in the pathogenesis of HIV dementia. This study used an in vitro model of the blood-brain barrier to determine the effects of ovine lentivirus (OvLV) infection on endothelial cells. The replication of two American OvLV isolates and two lcelandic OvLV isolates in pure cultures of endothelial cells isolated from brain was compared to replication in endothelial cells from adipose, lung, and aorta. Inoculation with the two American isolates resulted in 100 times greater reverse transcriptase (RT) activity in supernatant of the microvascular endothelial cells (brain, lung, and adipose) than in the macrovascular endothelial cells (aorta). Conversely, inoculation with the two lcelandic isolates resulted in 100 times higher RT activity in aortic, lung, and adipose endothelial cells than in the brain endothelial cells. Transmission electron microscopy of the brain capillary endothelial cells infected with the American isolates revealed polarized viral budding from the lateral cell membrane and a loss of tight junctions. Replication of OvLV in brain capillary endothelial cells could play a role in the pathogenesis of lentiviral encephalitis by altering blood-brain barrier integrity.
血脑屏障功能障碍被认为在HIV痴呆的发病机制中起重要作用。本研究使用血脑屏障的体外模型来确定绵羊慢病毒(OvLV)感染对内皮细胞的影响。将两种美国OvLV分离株和两种冰岛OvLV分离株在从脑部分离的内皮细胞纯培养物中的复制情况与在脂肪、肺和主动脉来源的内皮细胞中的复制情况进行比较。用两种美国分离株接种后,微血管内皮细胞(脑、肺和脂肪)上清液中的逆转录酶(RT)活性比大血管内皮细胞(主动脉)高100倍。相反,用两种冰岛分离株接种后,主动脉、肺和脂肪内皮细胞中的RT活性比脑内皮细胞高100倍。对感染美国分离株的脑毛细血管内皮细胞进行透射电子显微镜检查发现,病毒从细胞膜外侧极化出芽,紧密连接丧失。OvLV在脑毛细血管内皮细胞中的复制可能通过改变血脑屏障完整性在慢病毒脑炎的发病机制中起作用。