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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-8-11
pubmed:abstractText
Towards understanding the pathogenesis of HIV dementia, we molecularly cloned and sequenced human immundeficiency virus type 1 (HIV-1) gp160 genes from uncultured post-mortem tissues collected from a patient with HIV dementia. Sequences from bone marrow, lymph node, lung, and four regions of brain - the deep white matter, head of caudate, choroid plexus and meninges - were compared. Also included were gp160 sequences recovered from blood monocytes collected 5 months prior to death. Phylogenetic analyses showed that the sequences from deep white matter were more closely related to those from bone marrow, than to those from the other tissues, and moreover, were most closely related to sequences from the blood monocytes. These findings suggest trafficking of bone marrow-derived monocytes into the deep white matter during this late stage of infection. Another cluster included sequences from choroid plexus, meninges and lymph node, and interestingly, identical patterns of four or nine stop codons were shared among these tissues. These mutations appear to be the consequence of G-->A hypermutation, and could reflect independent events, or the movement of virions or infected cells, from the choroid plexus into the cerebrospinal fluid and ultimately, into the lymph node. We propose that a critical step towards the development of HIV dementia is an increase in monocyte trafficking into the brain, and that this process is either initiated and/or accelerated during late-stage infection, which could explain why dementia occurs primarily during this time.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1355-0284
pubmed:author
pubmed:issnType
Print
pubmed:volume
6 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S70-81
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10871768-AIDS Dementia Complex, pubmed-meshheading:10871768-Amino Acid Sequence, pubmed-meshheading:10871768-Brain, pubmed-meshheading:10871768-Cell Movement, pubmed-meshheading:10871768-Genes, Viral, pubmed-meshheading:10871768-HIV Envelope Protein gp160, pubmed-meshheading:10871768-HIV-1, pubmed-meshheading:10871768-Humans, pubmed-meshheading:10871768-Male, pubmed-meshheading:10871768-Middle Aged, pubmed-meshheading:10871768-Molecular Sequence Data, pubmed-meshheading:10871768-Monocytes, pubmed-meshheading:10871768-Organ Specificity, pubmed-meshheading:10871768-Phylogeny, pubmed-meshheading:10871768-Polymorphism, Genetic, pubmed-meshheading:10871768-Prospective Studies, pubmed-meshheading:10871768-Sequence Analysis, DNA, pubmed-meshheading:10871768-Sequence Homology, Amino Acid
pubmed:year
2000
pubmed:articleTitle
Analysis of human immunodeficiency virus type 1 gp160 sequences from a patient with HIV dementia: evidence for monocyte trafficking into brain.
pubmed:affiliation
Department of Neurology, The Johns Hopkins University, Baltimore, Maryland, MA 21287, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Multicenter Study