期刊
RETROVIROLOGY
卷 10, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1742-4690-10-101
关键词
ADAP; HIV-1 transcription; HIV-1 transmission; Integrin; Virological synapse
类别
资金
- Ministry of Science and Technology China [2012CB910800]
- National Natural Science Foundation of China [31370859, 31070778]
- Pujiang Program [2010-0000506]
- Key lab of Molecular Virology & Immunology in CAS
- Wellcome Trust
- Medical Research Council Career Development Award [G0800312]
- intra-European Marie Curie fellowship [220092]
- Medical Research Council [G0800312, G0800142] Funding Source: researchfish
- MRC [G0800142, G0800312] Funding Source: UKRI
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-kappa B 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.
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