SHIV1157ipd3N4小量多次阴道粘膜感染中国猕猴的初步研究

Efficient Repeated Low-dose Intravaginal Infection with SHIVl157ipd3N4 in Rhesus Monkey

目的建立R5-SHIV1157ipd3N4病毒中国猕猴阴道粘膜小剂量多次感染模型，为我国艾滋病疫苗有效性评价提供新的模型构建、应用策略。方法选用10—20TCID50剂量的SHIV1157ipd3N4病毒阴道黏膜途径感染6只雌性中国猕猴，共感染11次，每次攻毒间隔4～7d。定期测定血浆病毒载量和外周血CD4＋：CD8＋。结果6只中国猕猴经11次病毒攻击后，均建立系统性感染，血浆病毒载量呈阳性；CD4＋：CD8＋均有下降。结论初步建立了R5-SHIV1157ipd3N4中国猕猴阴道黏膜小剂量多次感染模型，为艾滋病研究提供了更接近于自然感染状态的模型建立模式。

Objective To establish a CCR5-specific chimeric simian/human immunodeficiency virus, SHIV 1157ipd3N4 repeated low-dose intravaginal infection model with rhesus monkeys. This new chimeric model could hopefully be more efficient model in AIDS vaccine development. Methods Six female Chinese rhesus monkeys were enrolled in this study. All animals were intra-vaginally challenged 11 times with 1 ml of a phosphate-buffer viral solution containing the heterologous SHIV1157ipd3N4, with 20 TCIDs0 for the first 3 challenges and 10 TCIDs0 for the remaining 8 challenges. Each challenge was accomplished at the interval of 4-7 days. Whole blood was collected and plasma virus was quantified by real-time SYBR Green RT-PCR and T cell subsets were determined by flow cytometry analysis. Results The systematic infection of six rhesus monkeys was established successfully after 11 challenges. The peaks of viral loads were between 10%opies/ml to 108copies/ml.Conclusion The repeated low-dose technique was used for establishing a SHIV1157ipd3N4 infection model of Chinese rhesus monkey. This model aliking sexual route would be very useful for HIV-1 subtype C vaccine and pathogenesis studies.