The adaptor protein SLP-76 regulates HIV-1 release and cell-to-cell transmission in T cells.
The adaptor protein SLP-76 regulates HIV-1 release and cell-to-cell transmission in T cells.
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DOI：
10.4049/jimmunol.1102106
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发表时间：
2012-03-15
期刊：
影响因子：
--
通讯作者：
Ganju RK
中科院分区：
文献类型：
--
作者：
Nagaraja T;Anand AR;Zhao H;Ganju RK
HIV-1 infection in T-cells is regulated by T-cell receptor (TCR) activation. However, the cellular proteins of the TCR pathway that regulate HIV-1 infection are poorly characterized. Here, we elucidated the role of SLP-76, a key adaptor protein of the TCR signaling complex, in HIV-1 infection. We observed a significant reduction of HIV-1 virus production in SLP-76-deficient Jurkat T-cells compared to wild-type and SLP-76-reconstituted Jurkat T-cells. We further confirmed the role of SLP-76 in HIV-1 infection by siRNA-mediated knockdown in MT4 cells and PBMCs. Structural-functional analysis revealed that the amino-terminal domain of SLP-76 was important for regulating HIV-1 infection. Further mechanistic studies revealed that lack of SLP-76 impaired virus release, but did not affect viral entry, integration and transcription. We also showed that SLP-76 plays a critical role in cell-to-cell transmission of HIV-1. Signaling studies revealed that SLP-76 associated with viral Nef protein and multiple signaling molecules during HIV-1 infection. Furthermore, SLP-76 facilitated the association of Nef and F-actin, suggesting that SLP-76 mediates the formation of a signaling complex that may regulate viral release via cytoskeletal changes. Taken together, our studies demonstrate a novel role for the adaptor molecule, SLP-76 in regulating HIV-1 infection in T-cells with potential to develop innovative strategies against HIV-1.
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DOI：
10.1084/jem.20012039
发表时间：
2002-04-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Manninen A;Saksela K
通讯作者：
Saksela K
DOI：
10.1007/978-1-59745-170-3_5
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Mbisa JL;Delviks-Frankenberry KA;Thomas JA;Gorelick RJ;Pathak VK
通讯作者：
Pathak VK
影响因子：
3.7
作者：
Neri, Francesca;Giolo, Giorgia;Doria, Margherita
通讯作者：
Doria, Margherita
影响因子：
11.4
作者：
Barda-Saad, Mira;Shirasu, Naoto;Samelson, Lawrence E.
通讯作者：
Samelson, Lawrence E.
影响因子：
64.5
作者：
Pivniouk, V;Tsitsikov, E;Geha, RS
通讯作者：
Geha, RS