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Published on: March 8, 2012
Slit2/Robo4 signaling modulates HIV-1 gp120-induced lymphatic hyperpermeability
Xuefeng Zhang1, Jinlong Yu, Paula M Kuzontkoski
1Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
Plos Pathogens
|January 14, 2012
Summary
Human immunodeficiency virus (HIV) envelope protein gp120 increases lymphatic permeability by disrupting Robo4 function. Targeting Slit2/Robo4 signaling may prevent HIV dissemination.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Human immunodeficiency virus (HIV) dissemination relies on viral and infected cell transit across lymphatic endothelium.
- The mechanism by which HIV alters lymphatic endothelial permeability remains largely unexplored.
Purpose of the Study:
- To investigate the mechanism of HIV-induced lymphatic hyperpermeability.
- To identify potential therapeutic targets for limiting HIV dissemination.
Main Methods:
- Utilized a primary human lymphatic endothelial cell model.
- Analyzed the effects of HIV-1 envelope protein gp120 on lymphatic endothelial cells.
- Investigated the role of Robo4 and Slit2/Robo4 signaling pathway.
Main Results:
- HIV-1 gp120 induced lymphatic hyperpermeability by disrupting Robo4 function.
- gp120 triggered fibronectin expression and integrin α₅β₁ phosphorylation, forming a complex that interacted with Robo4.
- Slit2, a Robo4 agonist, protected cells by inhibiting c-Src kinase activation.
Conclusions:
- HIV-1 gp120 disrupts lymphatic endothelial barrier integrity via the Slit2/Robo4 pathway.
- Targeting Slit2/Robo4 signaling presents a potential strategy to limit HIV dissemination.
