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Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors.
- Source :
-
Retrovirology . 2013, Vol. 10 Issue 1, p1-14. 14p. 5 Graphs. - Publication Year :
- 2013
-
Abstract
- 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 downregulation 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17424690
- Volume :
- 10
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Retrovirology
- Publication Type :
- Academic Journal
- Accession number :
- 127938960
- Full Text :
- https://doi.org/10.1186/1742-4690-10-101