B 亚型 SHIVSF162p3 中国恒河猴小剂量多次阴道黏膜感染
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1. 中国医学科学院医学实验动物研究所,卫生部人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室,北京 100021; 2. Mymetics Corporation,CH 1066 Epalinges,Switzerland

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Efficient Repeated Low-Dose Intravaginal Infection with SHIVSF162p3 in Chinese-Origin Rhesus Macaques
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1. Key Laboratory of Human Diseases Comparative Medicine,Ministry of Health; Institute of Medical Laboratory Animal Science,Chinese Academy of Medical Sciences; Key Laboratory of Human Diseases Animal Models,State Administration of Traditional Chinese Medicine,Beijing 100021,China;2. Mymetics Corporation,CH 1066 Epalinges,Switzerland

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    摘要:

    目的 模拟 HIV 性传播感染特点进行中国恒河猴阴道黏膜小剂量多次感染研究,为我国艾滋病疫苗有效性评价提供新的模型构建思路。方法 选用 20-30TCID50剂量的 SHIVSF162p3病毒阴道黏膜途径感染六只成年雌性中国恒河猴,共感染 13 次,每次攻毒间隔 4 ~ 7 d。采取测定血浆病毒载量和外周血 CD4 + ∶ CD8 + 。结果 6 只中国恒河猴经 13 次病毒攻击后,经检测均建立系统性感染,血浆病毒载量呈阳性;CD4 + ∶ CD8 + 均有下降。结论成功建立了中国恒河猴阴道黏膜小剂量多次感染模型,为艾滋病研究提供了新的更接近于自然感染状态的模型建立模式。

    Abstract:

    Objective Nonhuman primate models are increasingly used in the screening of candidate AIDS vaccines and immunization strategies for advancement to large-scale human trials. The predictive value of such macaque studies is largely dependent upon the fidelity of the model system in mimicking human immunodeficiency virustype 1 ( HIV-1) infection in terms of viral transmission,replication,and pathogenesis. The aim of this study was to establish a Chineseorigin rhesus monkey model of CCR5-specific chimeric simian / human immunodeficiency virus ( SHIVSF162p3 ) infection,induced by repeated low-dose intravaginal infection,and explore whether this new chimeric model could be more efficient in AIDS vaccine research. Methods Totally 6 female Chinese-origin rhesus monkeys were enrolled in this study. All animals were intra-vaginally challenged 13 times with 1 mL of a phosphate buffered virus solution containing the heterologous SHIVSF162p3,with 20 TCID50 for the first 7 challenges and 30 TCID50 for the remaining 6 challenges. Challenges were done every 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 Systemtic infection was successfully established in 6 Chinese-origin rhesus macaques after 13 challenges. The peak of viral loads was between 106 copies/mL to 108 copies/mL,wherease their CD4 + /CD8 + ratio was decreased. Conclusions The results of this study provide a firm basis for establishing a Chinese rhesus macaques model of SHIV infection by repeated low dose of SHIVSF162p3,a route more close to natural way of AIDS infection. This model would be very useful for HIV-1 subtype B vaccine and pathogenesis studies.

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丛 喆,刘 浩,朵建英,王 卫,蒋 虹,高 虹,杨志伟,Sylvain Fleury,魏 强,秦 川. B 亚型 SHIVSF162p3 中国恒河猴小剂量多次阴道黏膜感染[J].中国比较医学杂志,2011,21(2):44~48.

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  • 收稿日期:2010-10-08
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  • 在线发布日期: 2025-11-11
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