Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors

Retrovirology

Christopher E Rudd⁷  Hongyan Wang⁴  Clare Jolly²  Andrew Lever⁵  Jianhua Wang³  Rongrong Zhai³  Wei Gao⁶  Youg Raj Thaker⁴  Daina Lim⁴  Elisabetta Groppelli²  Truus E M Abbink¹  Lei Han⁶  Bin Wei⁶ 

[1] TEMA current address: Centre for Childhood White Matter Disorders, VU University Medical Centre, De Boelelaan 1087, 1081HV, Amsterdam, the Netherlands;Division of Infection and Immunity, University College London, London WC1E 6BT, UK;Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai China;Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK;Department of Medicine, Level 5, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK;The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China;Cambridge Institute of Medical Research, Hills Road, CB2 OXY, Cambridge, UK

关键词: Virological synapse;    Integrin;    HIV-1 transmission;    HIV-1 transcription;    ADAP;   

Others  :  807187
DOI  :  10.1186/1742-4690-10-101

 received in 2013-04-09, accepted in 2013-09-12,  发布年份 2013

【 摘 要 】

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-κB 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.

【 授权许可】

   
2013 Wei et al.; licensee BioMed Central Ltd.

【 图 表 】

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