9月18日,，Retrovirology在線發(fā)表了中科院上海生科院生物化學與細胞生物學研究所王紅艷研究組的研究成果Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors。該成果揭示了在HIV-1感染T細胞的過程中，免疫銜接蛋白ADAP通過參與不同共刺激分子CD28或LFA-1的信號通路,，分別調(diào)控HIV-1在T細胞內(nèi)的轉(zhuǎn)錄、HIV-1在樹突狀細胞DC-T細胞之間的播散,。
當T細胞受體（TCR）信號通路被激活后,，ADAP與上游信號分子SLP76結(jié)合，構(gòu)建TCR介導的inside-out信號通路,，導致T細胞表面整合素（integrin）粘附能力增強,，并促進T細胞活化。該研究發(fā)現(xiàn)：（1）在HIV-1感染的DC向未感染的T細胞播散病毒時,，降低T細胞中ADAP的表達或阻止SLP76-ADAP信號復合體,，通過抑制整合素LFA-1介導的病毒突觸（Virological Synapse）的形成，進而阻止HIV-1在免疫細胞間的傳播,；（2）T細胞的活化能促進HIV-1的感染,。當T細胞接受來自共刺激分子CD28的信號后，利用SLP76-ADAP信號復合體,，活化轉(zhuǎn)錄因子NF-κB,，促進HIV-1的轉(zhuǎn)錄。但此轉(zhuǎn)錄過程不依賴整合素LFA-1的活化,。該研究從宿主免疫細胞的角度出發(fā),，首次揭示免疫銜接蛋白ADAP利用不同信號通路，多環(huán)節(jié)參與HIV-1轉(zhuǎn)錄,、HIV-1在細胞間播散的感染過程,。這項研究提示靶向宿主免疫細胞中的SLP76-ADAP信號復合體，可能作為控制HIV-1感染的新靶點,。
該研究課題與英國劍橋大學Christopher E Rudd教授合作共同完成,，并獲得中科院上海巴斯德所王建華研究組的大力幫助。
該課題得到國家科技部,、國家自然科學基金委,、浦江人才計劃和中國科學院分子病毒與免疫重點實驗室的經(jīng)費支持（生物谷Bioon.com）。
生物谷推薦的英文摘要
Retrovirology doi:10.1186/1742-4690-10-101
Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors
Bin Wei,， Lei Han,， Truus E Abbink,， Elisabetta Groppelli， Daina Lim,， Youg Raj Thaker,， Wei Gao， Rongrong Zhai,， Jianhua Wang,， Andrew Lever， Clare Jolly,， Hongyan Wang and Christopher E Rudd
Background
Immune cell adaptor protein ADAP (adhesion and degranulation-promoting adaptor protein) mediates aspects of T-cell adhesion and proliferation. Despite this,， a connection between ADAP and infection by the HIV-1 (human immunodeficiency virus-1) has not been explored.
Results
In this paper， we show for the first time that ADAP and its binding to SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa) regulate HIV-1 infection via two distinct mechanisms and co-receptors. siRNA down-regulation of ADAP,， or expression of a mutant that is defective in associating to its binding partner SLP-76 (termed M12),， inhibited the propagation of HIV-1 in T-cell lines and primary human T-cells. In one step， ADAP and its binding to SLP-76 were needed for the activation of NF-kappaB and its transcription of the HIV-1 long terminal repeat (LTR) in cooperation with ligation of co-receptor CD28,， but not LFA-1. In a second step,， the ADAP-SLP-76 module cooperated with LFA-1 to regulate conjugate formation between T-cells and dendritic cells or other T-cells as well as the development of the virological synapse (VS) and viral spread between immune cells.
Conclusions
These findings indicate that ADAP regulates two steps of HIV-1 infection cooperatively with two distinct receptors， and as such,， serves as a new potential target in the blockade of HIV-1 infection.
