Gigout L, Vaslin B, Matheux F, Caufour P, Neildez O, Chéret A, Lebel-Binay S, Théodoro F, Dilda P, Benveniste O, Clayette P, Le Grand R, Dormont D
CEA, Service de Neurovirologie, DSV/DRM, CRSSA, Fontenay aux Roses, France.
Res Virol. 1998 Nov-Dec;149(6):341-54. doi: 10.1016/s0923-2516(99)80002-8.
This study evaluates the consequences of antiretroviral treatment of the acute simian immunodeficiency virus (SIV) primary infection on virus load and cytokine responses. Four cynomolgus macaques were inoculated intravenously with a pathogenic primary isolate (SIVmac251). Animals were pretreated with 10.8 mg/kg/day of dideoxyinosine (ddI) from 4 days before inoculation, and treatment was continued for 28 days. Proinflammatory (IL6, IL1 beta and TNF alpha) and antiinflammatory (IL10) cytokine and lymphokine (IL2, IL4 and IFN gamma) polymerase chain reaction (PCR) ratios were monitored in unmanipulated peripheral blood mononuclear cells (PBMCs) during acute infection by using a semiquantitative reverse transcription (RT)-PCR method. PBMC-associated virus loads were dramatically reduced compared to those of placebo-treated macaques. Nevertheless, a transient rise in IL6, IL1 beta, TNF alpha and IL10 mRNA expression was observed in PBMCs. IL2, IL4 and IFN gamma mRNAs were either undetectable or weakly detectable throughout the study, with no major changes. Despite a dramatic reduction in the acute viral loads in ddI-treated monkeys, early cytokine mRNA profiles were comparable to those of untreated SIVmac251-infected monkeys. Contrary to what was previously evidenced during primary infection with an attenuated SIV clone, no increase in IL2 and IL4 mRNA was detected in PBMCs of the ddI-treated monkeys, although these monkeys exhibited virus loads similar to those evidenced in macaques infected by attenuated SIV. These data indicate that differential lymphokine expression patterns found in pathogenic and Nef-truncated SIV-infected monkeys may not be strictly dependent on virus load levels.
本研究评估了抗逆转录病毒治疗急性猿猴免疫缺陷病毒（SIV）原发性感染对病毒载量和细胞因子反应的影响。4只食蟹猴静脉接种致病性原发性分离株（SIVmac251）。动物在接种前4天用10.8mg/kg/天的双脱氧肌苷（ddI）进行预处理，并持续治疗28天。在急性感染期间，通过使用半定量逆转录（RT）-PCR方法，监测未处理的外周血单个核细胞（PBMC）中促炎（IL6、IL1β和TNFα）和抗炎（IL10）细胞因子以及淋巴因子（IL2、IL4和IFNγ）的聚合酶链反应（PCR）比值。与安慰剂治疗的猕猴相比，PBMC相关病毒载量显著降低。然而，在PBMC中观察到IL6、IL1β、TNFα和IL10 mRNA表达短暂升高。在整个研究过程中，IL2、IL4和IFNγ mRNA要么检测不到，要么检测到的水平较弱，没有重大变化。尽管ddI治疗的猴子急性病毒载量显著降低，但早期细胞因子mRNA谱与未治疗的SIVmac251感染猴子的谱相当。与先前在感染减毒SIV克隆的原发性感染期间所证明的情况相反，在ddI治疗的猴子的PBMC中未检测到IL2和IL4 mRNA增加，尽管这些猴子的病毒载量与感染减毒SIV的猕猴中所证明的相似。这些数据表明，在致病性和Nef截短的SIV感染猴子中发现的不同淋巴因子表达模式可能并不严格依赖于病毒载量水平。
