Jordan E K, Heyes M P
Animal Health and Care Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
AIDS. 1993 Sep;7(9):1173-9. doi: 10.1097/00002030-199309000-00004.
In this 2.5-year study of simian immunodeficiency virus (SIVsm) infection in rhesus monkeys, quinolinic acid (QUIN) levels and virus isolation determinations were made in serial cerebrospinal fluid (CSF) and blood samples to evaluate the relationship between these parameters over the course of infection.
Eight rhesus monkeys were inoculated in the saphenous vein with SIVsm. Four animals were maintained as uninoculated controls. CSF and blood samples were obtained every 1-4 weeks over the course of study. SIV isolation was determined in H9 cells for the CSF and in primary rhesus lymphocyte co-cultures for peripheral blood mononuclear cells (PBMC). QUIN was quantitated in CSF and serum by electron-capture negative chemical ionization gas chromatography mass spectrometry.
All SIV-inoculated animals became CSF and PBMC isolation-positive by 1-3 weeks post-inoculation. Control animals remained SIV-negative. One SIV-positive animal was humanely euthanized at 2 weeks post-inoculation. The three SIV-inoculated animals that were CSF isolation-negative after the fifth week post-inoculation maintained CSF QUIN values < 100 nM, remained CSF and PBMC isolation-negative, and clinically healthy in the chronic course of disease. In contrast, the four SIV-inoculated animals that were CSF isolation-positive 6-8 weeks post-inoculation had CSF QUIN levels as high as 153-565 nM during the second month post-inoculation and remained CSF virus isolation-negative, persistently PBMC isolation-positive, and experienced clinical symptoms of SIV in the chronic course of disease. Three of these four animals have succumbed to SIV infection.
Initial QUIN responses and viral isolation status in the first month post-inoculation were consistent among SIV-inoculated animals with CSF and serum QUIN values significantly higher than those of controls. A divergence within the SIV-inoculated group of animals became apparent within the second month of primary SIV infection and was maintained throughout the course of infection. Persistent PBMC viral isolation and marked elevations of QUIN were linked to symptomatic disease and a poor prognosis for survival. Predominantly negative PBMC viral isolation and slight, but significant, elevations of QUIN were linked to asymptomatic disease with a favorable prognosis for survival.
在这项对恒河猴进行的为期2.5年的猿猴免疫缺陷病毒（SIVsm）感染研究中，对系列脑脊液（CSF）和血液样本进行喹啉酸（QUIN）水平及病毒分离测定，以评估感染过程中这些参数之间的关系。
8只恒河猴经隐静脉接种SIVsm。4只动物作为未接种对照。在研究过程中每1 - 4周采集CSF和血液样本。CSF的SIV分离在H9细胞中进行，外周血单核细胞（PBMC）的SIV分离在原代恒河猴淋巴细胞共培养物中进行。通过电子捕获负化学电离气相色谱 - 质谱法对CSF和血清中的QUIN进行定量。
所有接种SIV的动物在接种后1 - 3周CSF和PBMC分离均呈阳性。对照动物SIV检测仍为阴性。1只SIV阳性动物在接种后2周被人道处死。接种SIV后第5周CSF分离阴性的3只动物CSF中QUIN值<100 nM，CSF和PBMC分离持续阴性，在疾病慢性期临床健康。相比之下，接种SIV后6 - 8周CSF分离阳性的4只动物在接种后第二个月CSF中QUIN水平高达153 - 565 nM，CSF病毒分离持续阴性，PBMC持续分离阳性，在疾病慢性期出现SIV临床症状。这4只动物中有3只死于SIV感染。
接种SIV的动物在接种后第一个月的初始QUIN反应和病毒分离状态一致，CSF和血清QUIN值显著高于对照。在初次SIV感染的第二个月内，接种SIV的动物组内出现明显差异，并在整个感染过程中持续存在。PBMC病毒持续分离和QUIN显著升高与有症状疾病及不良生存预后相关。PBMC病毒分离主要为阴性以及QUIN轻微但显著升高与无症状疾病及良好生存预后相关。
