A human immunodeficiency virus-transgenic mouse model for assessing interventions that block microbial-induced proviral expression.
A human immunodeficiency virus-transgenic mouse model for assessing interventions that block microbial-induced proviral expression.
复制标题
人类免疫缺陷病毒转基因小鼠模型，用于评估阻断微生物诱导的原病毒表达的干预措施。
DOI：
10.1086/320716
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Sher,A
中科院分区：
文献类型：
--
作者：
Schito,ML;Kennedy,PE;Kowal,RP;Berger,EA;Sher,A
将先前在病原体感染后显示病毒蛋白和感染性颗粒表达上调的人类免疫缺陷病毒（HIV）1型转基因小鼠系（166）作为筛选HIV-1免疫活化抑制剂的体外和体内功效的模型进行测试。评估了两种类型的干预措施：使用免疫抑制药物泼尼松龙或HIV-1病毒靶向毒素（sCD 4-PE 40）。这两种药物在体外抑制脂多糖诱导的脾细胞p24表达，当给药转基因小鼠，抑制血浆p24的诱导，以及p24和感染性病毒的体外生产刺激体内感染鸟分枝杆菌。此外，在用任一药剂处理的小鼠中，脾脏中的HIV-1 mRNA水平大大降低。因为HIV-1表达不能在来自166系小鼠的T淋巴细胞中诱导，所以该模型对于测试针对非T细胞病毒储库的病毒产生的干预可能特别有利
A human immunodeficiency virus (HIV) type 1–transgenic mouse line (166) that previously showed up-regulated expression of viral proteins and infectious particles after infection with pathogenic agents was tested as a model for screening the in vitro and in vivo efficacy of inhibitors of HIV-1 immune activation. Two types of interventions were assessed: use of either the immunosuppressive drug prednisolone or an HIV-1 envelope–targeted toxin (sCD4-PE40). Both agents inhibited lipopolysaccharide-induced p24 expression by splenocytes in vitro and, when administered to transgenic mice, suppressed the induction of plasma p24, as well as the ex vivo production of p24 and infectious virus stimulated by in vivo infection withMycobacterium avium. Moreover, HIV-1 mRNA levels in the spleen were greatly reduced in mice treated with either agent. Because HIV-1 expression cannot be induced in T lymphocytes from line 166 mice, this model may be of particular advantage for testing interventions that target virus production by non–T cell virus reservoirs