Gruol D L, Yu N, Parsons K L, Billaud J N, Elder J H, Phillips T R
Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Neurovirol. 1998 Aug;4(4):415-25. doi: 10.3109/13550289809114540.
FIV is a lentivirus of domestic cats that causes neurologic disorders which are remarkably similar to those found in HIV-1 infected people. Using feline neuron cultures, we investigated the potential of both FIV virus and FIV-Env protein to cause neuronal damage through the excitotoxicity mechanism. The neuron swelling and lactate dehydrogenase (LDH) release assays were used as measures of cellular damage. The effects of FIV Env protein on glutamate receptor mediated increases in intracellular calcium were also examined. We found that FIV virus and FIV-Env protein significantly increased LDH release from the neuron cultures. Additionally, an increase in neuron size was detected in the cultures exposed to the virus, while swelling did not occur with exposure to either saline, denatured virus, or FIV-Env by itself. However, when both 20 microM glutamate and the FIV-PPR Env protein were added to the culture, a significant increase in neuron cell size was observed. The NMDA calcium signals were similar in general form between the control and FIV-PPR Env exposed cultures. However, the FIV - PPR Env protein treated cultures resulted in significant enhancement of the NMDA induced calcium signal. Our results indicate that FIV Env protein (either within the virion or baculovirus expressed) induced neurotoxicity as measured by neuron swelling and LDH release assays and that exposure of feline neurons to FIV Env protein alters the handling of intracellular calcium. These findings help to validate the FIV/cat system as a potential animal model for evaluating therapeutic approaches that target the excitotoxicity mechanisms of lentivirus induced CNS disease.
猫免疫缺陷病毒（FIV）是家猫的一种慢病毒，可引发与HIV - 1感染人群中发现的极为相似的神经疾病。我们利用猫神经元培养物，研究了FIV病毒和FIV包膜蛋白（FIV-Env蛋白）通过兴奋性毒性机制导致神经元损伤的可能性。神经元肿胀和乳酸脱氢酶（LDH）释放测定被用作细胞损伤的衡量指标。我们还检测了FIV Env蛋白对谷氨酸受体介导的细胞内钙增加的影响。我们发现，FIV病毒和FIV-Env蛋白显著增加了神经元培养物中LDH的释放。此外，在接触病毒的培养物中检测到神经元大小增加，而接触生理盐水、变性病毒或单独的FIV-Env时未出现肿胀。然而，当向培养物中同时添加20微摩尔谷氨酸和FIV-PPR Env蛋白时，观察到神经元细胞大小显著增加。在对照培养物和接触FIV-PPR Env的培养物之间，N-甲基-D-天冬氨酸（NMDA）钙信号的总体形式相似。然而，经FIV - PPR Env蛋白处理的培养物导致NMDA诱导的钙信号显著增强。我们的结果表明，通过神经元肿胀和LDH释放测定，FIV Env蛋白（无论是在病毒粒子内还是杆状病毒表达的）诱导了神经毒性，并且猫神经元接触FIV Env蛋白会改变细胞内钙的处理。这些发现有助于验证FIV/猫系统作为一种潜在的动物模型，用于评估针对慢病毒诱导的中枢神经系统疾病兴奋性毒性机制的治疗方法。
