dc.contributor.author | Zhang, Xeufeng | |
dc.contributor.author | Yu, JinLong | |
dc.contributor.author | Kuzontkoski, Paula Marie | |
dc.contributor.author | Zhu, Weiquan | |
dc.contributor.author | Li, Dean Y. | |
dc.contributor.author | Groopman, Jerome Elliot | |
dc.date.accessioned | 2012-08-08T14:38:45Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Zhang, Xuefeng, JinLong Yu, Paula M. Kuzontkoski, Weiquan Zhu, Dean Y. Li, and Jerome E. Groopman. 2012. Slit2/Robo4 signaling modulates HIV-1 gp120-induced lymphatic hyperpermeability. PLoS Pathogens 8(1): e1002461. | en_US |
dc.identifier.issn | 1553-7366 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:9369657 | |
dc.description.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 \(\alpha_5\beta_1\) 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. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | doi:10.1371/journal.ppat.1002461 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252370/pdf/ | en_US |
dash.license | LAA | |
dc.subject | medicine | en_US |
dc.subject | cardiovascular | en_US |
dc.subject | vascular biology | en_US |
dc.subject | infectious diseases | en_US |
dc.subject | viral diseases | en_US |
dc.subject | HIV | en_US |
dc.title | Slit2/Robo4 Signaling Modulates HIV-1 gp120-Induced Lymphatic Hyperpermeability | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS Pathogens | en_US |
dash.depositing.author | Yu, JinLong | |
dc.date.available | 2012-08-08T14:38:45Z | |
dc.identifier.doi | 10.1371/journal.ppat.1002461 | * |
dash.contributor.affiliated | Groopman, Jerome | |
dash.contributor.affiliated | Kuzontkoski, Paula Marie | |
dash.contributor.affiliated | Yu, Jinlong | |