Linked Life Data

19641037

Source:http://linkedlifedata.com/resource/pubmed/id/19641037

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-10-30
pubmed:abstractText
Lymphocyte trafficking is a multistep, intricate process and involves a number of host factors such as integrins and chemokine receptors on lymphocytes, adhesion molecules on endothelial cells, and chemokines present in the local microenvironment. Previous studies have shown that HIV-1 Nef inhibits T cell chemotaxis in response to the physiological ligand SDF-1alpha [( 1) ]. In this study, we aimed to gain a better understanding of the inhibitory mechanisms and to define the molecular determinants of HIV-1 Nef for this phenotype. We showed that HIV-1 Nef inhibited transwell and transendothelial migration of T cells. Specifically, HIV-1 Nef protein impaired T cell chemotaxis toward SDF-1alpha without altering CXCR4 expression. Moreover, we showed that HIV-1 Nef protein down-modulated LFA-1 expression on T lymphocytes and diminished adhesion and polarization of T lymphocytes and as a result, led to decreased migration across the endothelium. Furthermore, we showed that the myristoylation site and DeltaSD domain played important roles in Nef-mediated inhibition of transwell and transendothelial migration and polarization of T lymphocytes; however, different sites or domains were needed for Nef-mediated LFA-1 down-modulation and impaired adhesion of T lymphocyte. Taken together, these results demonstrated that HIV-1 Nef inhibited T lymphocyte migration at multiple steps and suggest that membrane localization and intracellular signaling events likely contribute to the inhibitory effects of Nef on T cell migration and subsequently, the pathobiology of the HIV-1 Nef protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1938-3673
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1171-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
HIV-1 Nef-mediated inhibition of T cell migration and its molecular determinants.
pubmed:affiliation
Center for AIDS Research and Department of Microbiology and Immunology, Indiana University School of Medicine, R2 302, 950 W. Walnut St., Indianapolis, IN 46202, USA. parki@iupui.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't