Mucosal transmission and induction of simian AIDS by CCR5-specific simian/human immunodeficiency virus SHIVSF162P3
Mucosal transmission and induction of simian AIDS by CCR5-specific simian/human immunodeficiency virus SHIVSF162P3
复制标题
DOI：
10.1128/jvi.75.4.1990-1995.2001
复制
发表时间：
2001-02-01
影响因子：
5.4
通讯作者：
Cheng-Mayer, C
中科院分区：
文献类型：
--
作者：
Harouse, JM;Gettie, A;Cheng-Mayer, C
非人灵长类动物模型越来越多地用于筛选候选艾滋病疫苗和免疫策略，以推进大规模人体试验。这种猕猴研究的预测价值在很大程度上取决于模型系统在模拟人类免疫缺陷病毒（HIV）1型感染的病毒传播，复制和发病机制方面的保真度。在这里，我们描述了有效的粘膜传输的CCR 5特异性嵌合猴/人类免疫缺陷病毒，SHIVSF 162 P3。在对子宫颈阴道粘膜单次无创伤应用后，用SHIVSF 162 P3感染雌性恒河猴。SHIVSF 162 P3感染猴的病程与自然HIV感染相似，在病毒复制、CD 4（+）外周血单核细胞的逐渐丧失和猿类AIDS定义的机会性感染的发展方面变化多样。SHIVSF 162 P3/猕猴模型应有助于直接临床前评估HIV疫苗策略，以及针对包膜靶细胞相互作用的抗病毒化合物。此外，这种受控模型提供了研究免疫应答和改变病毒传播和随后疾病进展的假定宿主特异性易感因素的环境。
Nonhuman primate models are increasingly used in the screening of candidate AIDS vaccine 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 virus (HIV) type 1 infection in terms of viral transmission, replication, and pathogenesis. Herein, we describe the efficient mucosal transmission of a CCR5-specific chimeric simian/human immunodeficiency virus, SHIVSF162P3. Female rhesus macaques were infected with SHIVSF162P3 after a single atraumatic application to the cervicovaginal mucosa. The disease course of SHIVSF162P3-infected monkeys is similar and as varied as natural HIV infection in terms of viral replication, gradual loss of CD4(+) peripheral blood mononuclear cells, and the development of simian AIDS-defining opportunistic infections. The SHIVSF162P3/macaque model should facilitate direct preclinical assessment of HIV vaccine strategies in addition to antiviral compounds directed towards envelope target cell interactions. Furthermore, this controlled model provides the setting to investigate immunologic responses and putative host-specific susceptibility factors that alter viral transmission and subsequent disease progression.