Horn T F, Huitron-Resendiz S, Weed M R, Henriksen S J, Fox H S
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15072-7. doi: 10.1073/pnas.95.25.15072.
Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction.
中枢神经系统(CNS)损伤和功能障碍是HIV感染的毁灭性后果。尽管中枢神经系统是HIV感染的初始靶标之一,但对于可能影响中枢神经系统功能的早期病毒诱导异常知之甚少。在此,我们报告在感染猿猴免疫缺陷病毒的猴子中检测到早期生理异常。急性感染导致昼夜节律紊乱,表现为体温升高,在接种后(p.i.)1至2周内,所有五只猴子均观察到体温升高,同时每日运动活动减少至对照水平的50%。在接种病毒后1个月和2个月时,动物仍处于高热状态,在接种病毒3个月后恢复到接种前的体温。尽管运动活动在接种后1个月恢复到基线值,但在接下来的2个月内,活动水平随后降至接种前值的约50%。对接种后1个月的感觉诱发电位进行分析发现,听觉诱发电位峰值潜伏期出现明显的感染诱导变化,这些变化在接种病毒3个月后仍然存在。这些早期生理异常可能先于可观察到的认知或运动缺陷的出现,并可为评估预防或减轻神经元功能障碍的药物提供一种检测方法。