Phipps A J, Hayes K A, Buck W R, Podell M, Mathes L E
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, USA.
J Acquir Immune Defic Syndr. 2000 Jan 1;23(1):8-16. doi: 10.1097/00126334-200001010-00002.
Although direct feline immunodeficiency virus (FIV) proviral DNA inoculation has been shown to be infectious in cats, long-term studies to assess the pathogenic nature of DNA inoculation are lacking. We have recently reported that direct feline leukemia virus (FeLV) DNA inoculation resulted in infection and the development of FeLV-related disease end points with similar temporal expression and virulence to that of cats infected with whole virus. We show in this study that pFIV-PPR DNA inoculation resulted in infection of cats and the development of FIV-related immunologic and neurologic abnormalities. Infected cats demonstrated progressive loss of CD4+ lymphocytes resulting in decreased CD4:CD8 ratios. Neurologic dysfunction was demonstrated by increased bilateral frontal lobe slow-wave activity. Prolongation of the visual evoked potential peak latency onset response pattern also supported a similar progression of abnormal cortical response. Furthermore, histopathologic examination revealed lesions attributed to FIV infection in lymph node, thymus, brain, and lung. Finally, nested polymerase chain reaction detected FIV provirus in brain, bone marrow, mesenteric lymph node, thymus, spleen, tonsil, and liver. These results confirm that FIV DNA inoculation is an efficient model for study of the pathogenic nature of molecular clones in vivo and offers the opportunity to measure temporal genomic stability of a homogeneous challenge material.
尽管直接接种猫免疫缺陷病毒(FIV)前病毒DNA已被证明在猫中具有传染性,但缺乏评估DNA接种致病性质的长期研究。我们最近报道,直接接种猫白血病病毒(FeLV)DNA会导致感染,并出现与感染全病毒的猫具有相似时间表达和毒力的FeLV相关疾病终点。我们在本研究中表明,接种pFIV-PPR DNA会导致猫感染,并出现与FIV相关的免疫和神经异常。受感染的猫表现出CD4+淋巴细胞逐渐减少,导致CD4:CD8比值降低。双侧额叶慢波活动增加证明了神经功能障碍。视觉诱发电位峰值潜伏期起始反应模式的延长也支持了异常皮质反应的类似进展。此外,组织病理学检查发现淋巴结、胸腺、脑和肺中存在归因于FIV感染的病变。最后,巢式聚合酶链反应在脑、骨髓、肠系膜淋巴结、胸腺、脾、扁桃体和肝脏中检测到FIV前病毒。这些结果证实,接种FIV DNA是研究体内分子克隆致病性质的有效模型,并提供了测量同质攻击材料时间基因组稳定性的机会。