Yu N, Billaud J N, Phillips T R
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2624-9. doi: 10.1073/pnas.95.5.2624.
Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that causes a spectrum of diseases remarkably similar to AIDS in HIV-infected humans. As part of this spectrum, both HIV-1 and FIV induce neurologic disorders. Because astrocytes are essential in maintaining the homeostasis of the central nervous system, we analyzed FIV for the ability to infect feline astrocytes. Through immunocytochemistry and reverse transcriptase activity, it was demonstrated that two molecular clones of FIV (FIV-34TF10 and FIV-PPR) produce a chronic low level productive infection of feline astrocyte cultures. To investigate the consequences of this infection, selected astrocyte functions were examined. Infection with FIV-34TF10 significantly decreased the ability of astrocytes to scavenge extracellular glutamate (with a peak inhibition of 74%). The effects of the infection did not appear to be a result of toxicity but rather were more selective in nature because the glucose uptake function of the infected astrocyte cultures was not altered. Our data demonstrate that FIV productively infected, at a low level, feline astrocyte cultures, and as a consequence of this infection, an important astroglial function was altered. These findings suggest that a chronic low grade infection of astrocytes may impair the ability of these cells to maintain homeostasis of the central nervous system that, in turn, may contribute to a neurodegenerative disease process that is often associated with lentivirus infections.
猫免疫缺陷病毒(FIV)是家猫的一种慢病毒,可引发一系列与人类感染HIV后的艾滋病极为相似的疾病。在这一系列病症中,HIV-1和FIV都会诱发神经紊乱。由于星形胶质细胞对于维持中枢神经系统的稳态至关重要,我们分析了FIV感染猫星形胶质细胞的能力。通过免疫细胞化学和逆转录酶活性检测,结果表明FIV的两个分子克隆(FIV-34TF10和FIV-PPR)可在猫星形胶质细胞培养物中引发慢性低水平的增殖性感染。为了研究这种感染的后果,我们检测了选定的星形胶质细胞功能。感染FIV-34TF10显著降低了星形胶质细胞清除细胞外谷氨酸的能力(最大抑制率为74%)。感染的影响似乎并非毒性所致,而是更具选择性,因为受感染的星形胶质细胞培养物的葡萄糖摄取功能未发生改变。我们的数据表明,FIV可在低水平上有效感染猫星形胶质细胞培养物,并且这种感染会导致一种重要的星形胶质细胞功能发生改变。这些发现表明,星形胶质细胞的慢性低度感染可能会损害这些细胞维持中枢神经系统稳态的能力,进而可能促成通常与慢病毒感染相关的神经退行性疾病进程。