Raymond L A, Wallace D, Berman N E, Marcario J, Foresman L, Joag S V, Raghavan R, Narayan O, Cheney P D
Department of Molecular & Integrative Physiology, Smith Mental Retardation and Human Development Research Centre, University of Kansas Medical Center, Kansas City 66160, USA.
J Neurovirol. 1998 Oct;4(5):512-20. doi: 10.3109/13550289809113495.
Nine rhesus macaques (Macaca mulatta) were inoculated with a combination of two passaged strains of SIVmac (R71 and 17E), both of which are known to be neurovirulent. Auditory brainstem responses (ABRs) were recorded at regular intervals from these animals both before and after inoculation. Increases in ABR peak and interpeak latency were observed corresponding to progression of SIV disease. Post-inoculation increases in latency were observed for all five peaks of the ABR and for interpeak intervals I-V and III-V. The largest increases in latency were associated with end-stage disease. Within 14 weeks of inoculation, all but two animals developed end-stage simian AIDS and were euthanized. Histopathological examination revealed multifocal lesions in the cerebral gray and white matter as well as in the auditory structures of the brainstem. In most animals, ABR changes were accompanied by evidence of underlying neuropathology. However, cases of severe neuropathology with no ABR abnormalities and vice versa were also noted. Though in a much shorter time frame, SIVmac R71/17E produced both physiological and histopathological abnormalities similar to those associated with HIV disease in humans. These results further support the SIVmac R71/17E infected rhesus macaque as an animal model of HIV related neurological disease in humans.
九只恒河猴(猕猴)接种了两种传代的猴免疫缺陷病毒(SIVmac)毒株(R71和17E)的组合,已知这两种毒株都具有神经毒性。在接种前后定期记录这些动物的听觉脑干反应(ABR)。观察到ABR峰值和峰间潜伏期的增加与SIV疾病的进展相对应。接种后,ABR的所有五个峰值以及峰间间期I-V和III-V的潜伏期均出现增加。潜伏期增加最大的与终末期疾病相关。在接种后的14周内,除两只动物外,所有动物均发展为终末期猴艾滋病并被安乐死。组织病理学检查显示大脑灰质和白质以及脑干听觉结构存在多灶性病变。在大多数动物中,ABR变化伴有潜在神经病理学的证据。然而,也注意到了严重神经病理学但无ABR异常的病例,反之亦然。尽管时间框架短得多,但SIVmac R71/17E产生了与人类HIV疾病相关的生理和组织病理学异常。这些结果进一步支持了感染SIVmac R71/17E的恒河猴作为人类HIV相关神经疾病的动物模型。