Recent research reveals that HIV infection is established within complexes of immune cells termed the "immune synapse." These immune units efficiently pass virus to uninfected cells and promote its transmission via lymphatic endothelial channels through the host. Several surface receptors act to pass and propagate HIV at the immune synapse, and no current therapy exists to abrogate HIV transmission at this biological complex. We propose an innovative strategy to target a novel ligand-receptor system, Slit/Robo that can block several of the facilitating receptors in the immune synapse. This ligand-receptor pair, we hypothesize, can be uniquely exploited to inhibit HIV passage between cells and HIV spread via lymphatic endothelial channels. We further postulate that this innovative therapeutic approach could be counteracted by cannabinoids, negating its benefit in certain drug abusers. This concern may paradoxically open up a synergistic way to enhance HIV inhibition by Slit/Robo at the immune synapse by additionally blocking relevant cannabinoid receptors. This proposal imagines containing and targeting HIV in restricted anatomic sites and would be a paradigm shift in how HIV/AIDS can be treated.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
5DP1DA026197-05
Application #
8306236
Study Section
Special Emphasis Panel (ZDA1-NXR-B (26))
Program Officer
Sorensen, Roger
Project Start
2008-09-05
Project End
2013-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$800,256
Indirect Cost
$329,517
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Yu, Jinlong; Zhang, Xuefeng; Kuzontkoski, Paula M et al. (2014) Slit2N and Robo4 regulate lymphangiogenesis through the VEGF-C/VEGFR-3 pathway. Cell Commun Signal 12:25