Synergistic effect of human CycT1 and CRM1 on HIV-1 propagation in rat T cells and macrophages.
Synergistic effect of human CycT1 and CRM1 on HIV-1 propagation in rat T cells and macrophages.
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DOI：
10.1186/1742-4690-6-43
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发表时间：
2009-05-12
期刊：
影响因子：
3.3
通讯作者：
Shida H
中科院分区：
文献类型：
--
作者：
Okada H;Zhang X;Ben Fofana I;Nagai M;Suzuki H;Ohashi T;Shida H
由于缺乏对HIV-1感染高度敏感的免疫活性小动物模型，HIV-1发病机制的体内研究和抗病毒策略的测试受到阻碍。尽管表达HIV-1受体复合物hCD 4和hCCR 5的转基因大鼠容易感染，但HIV-1在这些动物中的复制能力非常差。为了证明开发更好的HIV-1感染大鼠模型的分子基础，我们使用已建立的细胞系和从hCycT 1/hCRM 1转基因大鼠制备的原代细胞来评估人细胞周期蛋白T1（hCycT 1）和CRM 1（hCRM 1）对大鼠T细胞和巨噬细胞中Gag p24产生的影响。在大鼠T细胞中，hCycT 1的表达使Gag产生增加20-50倍，但在巨噬细胞中几乎没有影响。hCRM 1的表达在巨噬细胞中使Gag产生增加10-15倍，但在T细胞中仅略微增加。这两种因子的表达协同增强了p24的产生，使其达到人类细胞中检测到的水平的约10-40%。在大鼠T细胞和巨噬细胞中产生的R5病毒是完全感染性的。hCycT 1和hCRM 1的表达似乎是开发支持HIV-1稳健繁殖的大鼠模型的基础。
In vivo studies of HIV-1 pathogenesis and testing of antiviral strategies have been hampered by the lack of an immunocompetent small animal model that is highly susceptible to HIV-1 infection. Although transgenic rats that express the HIV-1 receptor complex hCD4 and hCCR5 are susceptible to infection, HIV-1 replicates very poorly in these animals. To demonstrate the molecular basis for developing a better rat model for HIV-1 infection, we evaluated the effect of human CyclinT1 (hCycT1) and CRM1 (hCRM1) on Gag p24 production in rat T cells and macrophages using both established cell lines and primary cells prepared from hCycT1/hCRM1 transgenic rats. Expression of hCycT1 augmented Gag production 20–50 fold in rat T cells, but had little effect in macrophages. Expression of hCRM1 enhanced Gag production 10–15 fold in macrophages, but only marginally in T cells. Expression of both factors synergistically enhanced p24 production to levels approximately 10–40% of those detected in human cells. R5 viruses produced in rat T cells and macrophages were fully infectious. The expression of both hCycT1 and hCRM1 appears to be fundamental to developing a rat model that supports robust propagation of HIV-1.
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影响因子：
64.5
作者：
Fornerod, M;Ohno, M;Mattaj, IW
通讯作者：
Mattaj, IW
影响因子：
30.3
作者：
Goffinet, Christine;Allespach, Ina;Keppler, Oliver T.
通讯作者：
Keppler, Oliver T.
影响因子：
4.9
作者：
Giuffre, AC;Higgins, J;North, TW
通讯作者：
North, TW
影响因子：
3.7
作者：
Koito, A;Shigekane, H;Matsushita, S
通讯作者：
Matsushita, S
影响因子：
3.3
作者：
Michel, Nico;Goffinet, Christine;Keppler, Oliver T.
通讯作者：
Keppler, Oliver T.