Phillips T R, Prospero-Garcia O, Wheeler D W, Wagaman P C, Lerner D L, Fox H S, Whalen L R, Bloom F E, Elder J H, Henriksen S J
Neuropharmacology, Scripps Research Institute, La Jolla California 92037, USA.
J Neurovirol. 1996 Dec;2(6):388-96. doi: 10.3109/13550289609146904.
FIV is a lentivirus of domestic cats that causes a spectrum of diseases that is remarkably similar to the clinical syndrome produced by HIV infection in people. Both HIV and FIV has been shown to cause neurologic dysfunction. Specific Pathogen-Free (SPF) cats were placed into one of three groups: FIV-PPR infected; DU-FIV-PPR (a dUTPase mutant of the FIV-PPR clone) infected; or an age-matched control group. In both infected groups, the general clinical signs of infection included lymphadenopathy, oral ulcerations, rough hair coat, and conjuntivitis. Specific neurological changes in the FIV-PPR infected cats included hind limb paresis; delayed righting and pupillary reflexes; behavioral changes; delayed visual and auditory evoked potentials; decreased spinal and peripheral nerve conduction velocities; and marked alterations in sleep patterns. Most of these changes were also observed in the DU-FIV-PPR infected cats. However, these cats tended to have a slightly less severe disease. In this study, we have demonstrated that an infectious molecular clone of FIV closely parallels the disease course of wild type FIV-infected cats. By using a knockout gene mutant of this clone, we were able to demonstrate that the dUTPase gene is not essential for neuropathogenesis. Further use of the FIV-PPR clone should prove useful in determining the essential viral elements that are important in the neuropathogenesis of lentiviral infections.
猫免疫缺陷病毒(FIV)是家猫的一种慢病毒,可引发一系列疾病,这些疾病与人类感染人类免疫缺陷病毒(HIV)所产生的临床综合征极为相似。研究表明,HIV和FIV均可导致神经功能障碍。将无特定病原体(SPF)猫分为三组:感染FIV-PPR组;感染DU-FIV-PPR(FIV-PPR克隆的dUTPase突变体)组;或年龄匹配的对照组。在两个感染组中,感染的一般临床症状包括淋巴结病、口腔溃疡、毛发粗糙和结膜炎。FIV-PPR感染猫的特定神经变化包括后肢轻瘫;翻正反射和瞳孔反射延迟;行为改变;视觉和听觉诱发电位延迟;脊髓和外周神经传导速度降低;以及睡眠模式的显著改变。在DU-FIV-PPR感染的猫中也观察到了这些变化中的大多数。然而,这些猫的病情往往略轻。在本研究中,我们证明了FIV的感染性分子克隆与野生型FIV感染猫的病程密切相似。通过使用该克隆的基因敲除突变体,我们能够证明dUTPase基因对于神经病理发生并非必需。进一步使用FIV-PPR克隆在确定慢病毒感染神经病理发生中重要的必需病毒元件方面应会证明是有用的。