中国恒河猴SIVmac239艾滋病模型急性期的试验观察

Experimental Observation of Simian Immunodeficiency Virus mac239 Chinese Rhesus Monkey Model at Acute Phase of Acquired Immune Deficiency Syndrome

【目的】复制猴免疫缺陷病毒(SIV)mac239中国恒河猴艾滋病模型,观察该动物模型急性期的变化特征,为中国恒河猴动物模型应用于艾滋病研究的标准化建立补充急性期变化内容。【方法】对15只健康中国恒河猴进行静脉接种SIVmac239病毒株复制中国恒河猴艾滋病动物模型,观察感染后10周内体质量指数(body mass index,BMI)、病毒载量、T淋巴细胞亚群指标变化情况及临床症状。【结果】健康恒河猴接种病毒株后10周内体质量及BMI指数比较稳定,各时间点比较无显著差异,其变化特征与艾滋病消耗综合症时期不同。感染第3天采用荧光定量PCR法检测,结果显示:在感染第10～14天病毒载量达到高峰,此后整体表现为水平波动下降趋势。T淋巴细胞亚群在感染后出现显著改变,其中CD3%、CD3计数整体表现为波动上升趋势;CD4%与CD4计数变化并不一致,感染后CD4%出现下降趋势,但CD4计数却出现增加趋势;CD8%、CD8计数均表现为波动上升趋势;CD4/CD8比值于感染后2周内明显下降,一般在病毒载量高峰时表现为最低比值,随后比值缓慢波动上升。感染10周内共有3只感染猴临床症状明显,其中1只出现腹泻、2只出现摄食下降等临床症状。【结论】中国恒河猴艾滋病动物模型与国外印度恒河猴艾滋病动物模型急性期相似,可用作急性期艾滋病模型动物。

Abstract： Objective To reproduce the simian immunodeficiency virus （SIV） mac239 Chinese rhesus monkey model of acquired immune deficiency syndrome （AIDS） in the acute phase and to investigate its characteristics at the acute phase of AIDS infection, thus to provide evidence of AIDS at the acute phase for the establishment of standardization of Chinese Rhesus monkeys used in the research. Methods Fifteen healthy Chinese rhesus monkeys were inoculated intravenously with SIVmac239 virus strains to reproduce Chinese rhesus monkey model of AIDS. The changes of body mass index （ BMI）, the viral load, T lymphocyte subsets and clinical symptoms wereobserved for 10 weeks after infection. Results During the 10 weeks after SIV acute infection, body weight and BMI index were relatively stable, the difference was not significant at all time points, which was different from AIDS at consumption phase. The results of real-time polymerase chain reaction （PCR） showed SIV was positive on day 3 of infection, the viral load reaches a peak on day 10-14 and after that showed a declining trend. T lymphocyte subsets showed significant changes after infection. Among them, CD3 % and CD3 count fluctuated and presented increasing trend. The changes of CD4 % and CD4 count were not synchronized, CD4 % had declining trend while the CD4 count was in an increasing trend after the infection. CD8 % and CD8 count fluctuate and were in upward trend, and the ratio of CD4 to CD8 decreased obviously within 2 weeks after infection, reached the bottom when the viral load was in peak value, and then increased slowly. Three rhesus monkeys had significant clinical symptoms within 10 weeks after the infection, one had diarrhea and two had the decrease of food intake. Conclusion The characteristics of Chinese rhesus monkey AIDS model and India rhesus monkey AIDS animal model are similar at the acute phase, indicating that SIV mac239 Chinese rhesus monkey AIDS model can be used as the experimental animal model for the research of AIDS at acute phase.