Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory.
Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory.
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DOI：
10.1016/j.nbd.2012.08.007
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发表时间：
2013-01
影响因子：
6.1
通讯作者：
Noel RJ Jr
中科院分区：
文献类型：
--
作者：
Chompre G;Cruz E;Maldonado L;Rivera-Amill V;Porter JT;Noel RJ Jr
尽管广泛使用抗逆转录病毒疗法可以有效限制病毒复制，但记忆障碍仍然是艾滋病毒感染者的一个困境。在中枢神经系统中，星形胶质细胞的 HIV 感染导致 HIV-1 Nef 蛋白的产生，而无需病毒复制。尸检研究发现，患有 HIV 相关痴呆症的人的海马星形胶质细胞中存在 Nef 表达，这表明即使病毒复制受到抑制，星形胶质细胞 Nef 也可能导致 HIV 相关认知障碍。为了测试 Nef 的星形胶质细胞表达是否足以诱导认知缺陷，我们检查了将表达 Nef 的原代大鼠星形胶质细胞植入海马体对空间和识别记忆的影响。与植入表达绿色荧光蛋白（GFP）的星形胶质细胞的对照组相比，单侧植入表达 Nef 的星形胶质细胞的大鼠表现出新位置和新物体识别能力受损。这种损伤与趋化因子配体 2 (CCL2) 表达的增加以及注射部位外周巨噬细胞浸润到海马相关。此外，暴露于 Nef 的大鼠表现出双侧 CA3 神经元缺失。这些结果表明，植入的星形胶质细胞表达的 Nef 蛋白会激活免疫系统，导致神经元损伤以及空间和识别记忆缺陷。因此，在没有病毒复制的情况下，星形胶质细胞持续表达 Nef 有可能导致 HIV 相关的认知障碍。
Despite the widespread use of antiretroviral therapy that effectively limits viral replication, memory impairment remains a dilemma for HIV infected people. In the CNS, HIV infection of astrocytes leads to the production of the HIV-1 Nef protein without viral replication. Post mortem studies have found Nef expression in hippocampal astrocytes of people with HIV associated dementia suggesting that astrocytic Nef may contribute to HIV associated cognitive impairment even when viral replication is suppressed. To test whether astrocytic expression of Nef is sufficient to induce cognitive deficits, we examined the effect of implanting primary rat astrocytes expressing Nef into the hippocampus on spatial and recognition memory. Rats implanted unilaterally with astrocytes expressing Nef showed impaired novel location and novel object recognition in comparison with controls implanted with astrocytes expressing green fluorescent protein (GFP). This impairment was correlated with an increase in chemokine ligand 2 (CCL2) expression and the infiltration of peripheral macrophages into the hippocampus at the site of injection. Furthermore, the Nef exposed rats exhibited a bilateral loss of CA3 neurons. These results suggest that Nef protein expressed by the implanted astrocytes activates the immune system leading to neuronal damage and spatial and recognition memory deficits. Therefore, the continued expression of Nef by astrocytes in the absence of viral replication has the potential to contribute to HIV associated cognitive impairment.
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DOI：
10.2174/1874357900802010024
发表时间：
2008
期刊：
The open virology journal
影响因子：
--
作者：
Fiala M;Singer EJ;Commins D;Mirzapoiazova T;Verin A;Espinosa A;Ugen K;Bernas M;Witte M;Weinand M;Lossinsky AS
通讯作者：
Lossinsky AS
影响因子：
3.2
作者：
Heaton, Robert K.;Franklin, Donald R.;Ellis, Ronald J.;McCutchan, J. Allen;Letendre, Scott L.;LeBlanc, Shannon;Corkran, Stephanie H.;Duarte, Nichole A.;Clifford, David B.;Woods, Steven P.;Collier, Ann C.;Marra, Christina M.;Morgello, Susan;Mindt, Monica Rivera;Taylor, Michael J.;Marcotte, Thomas D.;Atkinson, J. Hampton;Wolfson, Tanya;Gelman, Benjamin B.;McArthur, Justin C.;Simpson, David M.;Abramson, Ian;Gamst, Anthony;Fennema-Notestine, Christine;Jernigan, Terry L.;Wong, Joseph;Grant, Igor
通讯作者：
Grant, Igor
影响因子：
3.2
作者：
Fischer-Smith T;Bell C;Croul S;Lewis M;Rappaport J
通讯作者：
Rappaport J
DOI：
10.1016/s0960-5428(06)80269-x
发表时间：
1994-01-01
期刊：
ADVANCES IN NEUROIMMUNOLOGY
影响因子：
--
作者：
CONANT, K;TORNATORE, C;MAJOR, EO
通讯作者：
MAJOR, EO
影响因子：
1.7
作者：
Koutsilieri, E;Czub, S;Riederer, P
通讯作者：
Riederer, P