Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-9-28
pubmed:abstractText
Human immunodeficiency virus (HIV)-1 within the CNS induces neuro-acquired immunodeficiency syndrome and acts as a reservoir for reinfection of peripheral tissues. HIV-1 crosses the blood-brain barrier (BBB) within infected immune cells and as cell-free virus by a CD4-independent mechanism. Which proteins control free virus transport across the BBB are unknown, but work with wheatgerm agglutinin (WGA) and heparin suggests that heparan sulfate proteoglycans, sialic acid, and N-acetyl-beta-D-glucosaminyl acid bind HIV-1. Here, we found that an HIV-1 T-tropic virus was taken up by mouse brain endothelial cells in vitro and crossed the BBB in vivo and could be effluxed as intact virus. Uptake was stimulated by WGA and protamine sulfate (PS) and inhibited by heparin. BBB uptake of virus involved four distinguishable binding sites: i) reversible cell surface binding involving gp120 and sensitive to PS/heparin but insensitive to WGA; internalization with a ii) WGA-sensitive site binding gp120 and iii) a PS/heparin-sensitive site not involving gp120; iv) membrane incorporation not affected by WGA, heparin, or PS. In conclusion, binding, internalization, and membrane incorporation are separately regulated steps likely determining whether HIV-1 is incorporated into brain endothelial cells, transported across them, or returned to the circulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-53
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Binding, internalization, and membrane incorporation of human immunodeficiency virus-1 at the blood-brain barrier is differentially regulated.
pubmed:affiliation
GRECC, Veterans Affairs Medical Center-St. Louis and St. Louis University School of Medicine, Division of Geriatrics, Department of Internal Medicine, St. Louis, MO 63106, USA. bankswa@slu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.