Mice transgenic for monocyte-tropic HIV type 1 produce infectious virus and display plasma viremia: a new in vivo system for studying the postintegration phase of HIV replication.
Mice transgenic for monocyte-tropic HIV type 1 produce infectious virus and display plasma viremia: a new in vivo system for studying the postintegration phase of HIV replication.
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单核细胞嗜性 HIV 1 型转基因小鼠产生感染性病毒并表现出血浆病毒血症：一种用于研究 HIV 复制整合后阶段的新体内系统。
DOI：
10.1089/088922200309142
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发表时间：
2000
影响因子：
1.5
通讯作者：
Goldstein,H
中科院分区：
文献类型：
--
作者：
BrowningPaul,J;Wang,EJ;Pettoello-Mantovani,M;Raker,C;Yurasov,S;Goldstein,MM;Horner,JW;Chan,J;Goldstein,H
为了建立一个用于研究HIV-1整合后复制阶段的体内系统，构建了一株嗜单核细胞的HIV-1分离物HIV-1JR-C SF全长感染性原病毒克隆的转基因小鼠系。来自两种独立的JR-CSF转基因小鼠系的白细胞产生感染人类pbmc的HIV-1。在这些小鼠中检测到的血浆病毒血症水平（平均600,000 HIV RNA拷贝/ml）与报道的HIV-1感染者相当。在用超级抗原葡萄球菌肠毒素B治疗或感染结核分枝杆菌后，这些小鼠体内的HIV RNA水平增加了几倍。因此，在LTR的控制下，原病毒编码嗜单核细胞的HIV-1毒株，在小鼠中以转基因形式表达，可以通过整合后复制阶段产生感染性病毒。此外，血浆病毒血症的存在可以通过测量血浆HIV-1 RNA水平来监测，这使得这些小鼠可以用于研究不同干预措施对调节体内HIV-1产生的影响。因此，这些小鼠提供了一种新的可操作系统来研究它们通过激活免疫系统的因子对HIV-1产生的体内调节。此外，该小鼠系统应该有助于描述人类特异性因子在调节HIV-1复制中的作用，并研究靶向HIV-1复制整合后阶段的药物的体内治疗效果。
To generate anin vivosystem for investigating the postintegration phase of HIV-1 replication, mouse lines transgenic for a full-length infectious proviral clone of a monocyte-tropic HIV-1 isolate, HIV-1JR-C SF, were constructed. Leukocytes from two independent JR-CSF transgenic mouse lines produced HIV-1 that infected human PBMCs. Plasma viremia was detected in these mice at levels (mean, >60,000 HIV RNA copies/ml) comparable to those reported for HIV-1-infected individuals. The levels of HIV RNA in these mice increased several-fold after either treatment with the superantigenStaphylococcusenterotoxin B or infection withMycobacterium tuberculosis. Thus, a provirus encoding a monocyte-tropic HIV-1 strain under the control of its LTR expressed as a transgene in mice can proceed through the postintegration replication phase and produce infectious virus. In addition, the presence of plasma viremia that can be monitored by measuring plasma HIV1 RNA levels permits these mice to be used to study the impact of different interventions on modulating in vivo HIV-1 production. Therefore, these mice provide a novel manipulable system to investigate thein vivoregulation of HIV-1 production by factors that activate the immune system. Furthermore, this murine system should be useful in delineating the role of human-specific factors in modulating HIV-1 replication and investigating thein vivotherapeutic efficacy of agents that target the postintegration stages of HIV-1 replication.