Abstract:
:Dissemination of HIV in the host involves transit of the virus and virus-infected cells across the lymphatic endothelium. HIV may alter lymphatic endothelial permeability to foster dissemination, but the mechanism is largely unexplored. Using a primary human lymphatic endothelial cell model, we found that HIV-1 envelope protein gp120 induced lymphatic hyperpermeability by disturbing the normal function of Robo4, a novel regulator of endothelial permeability. HIV-1 gp120 induced fibronectin expression and integrin α₅β₁ phosphorylation, which led to the complexing of these three proteins, and their subsequent interaction with Robo4 through its fibronectin type III repeats. Moreover, pretreatment with an active N-terminus fragment of Slit2, a Robo4 agonist, protected lymphatic endothelial cells from HIV-1 gp120-induced hyperpermeability by inhibiting c-Src kinase activation. Our results indicate that targeting Slit2/Robo4 signaling may protect the integrity of the lymphatic barrier and limit the dissemination of HIV in the host.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Zhang X,Yu J,Kuzontkoski PM,Zhu W,Li DY,Groopman JEdoi
10.1371/journal.ppat.1002461subject
Has Abstractpub_date
2012-01-01 00:00:00pages
e1002461issue
1eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-11-00758journal_volume
8pub_type
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