Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2006-11-6
pubmed:databankReference
pubmed:abstractText
A novel 2986-base transcript encoded by the antisense strand of the HRES-1 human endogenous retrovirus was isolated from peripheral blood lymphocytes. This transcript codes for a 218-amino acid protein, termed HRES-1/Rab4, based on homology to the Rab4 family of small GTPases. Antibody 13407 raised against recombinant HRES-1/Rab4 detected a native protein of identical molecular weight in human T cells. HRES-1 nucleotides 2151-1606, located upstream of HRES-1/Rab4 exon 1, have promoter activity when oriented in the direction of HRES-1/Rab4 transcription. The human immunodeficiency virus, type 1 (HIV-1), tat gene stimulates transcriptional activity of the HRES-1/Rab4 promoter via trans-activation of the HRES-1 long terminal repeat. Transfection of HIV-1 tat into HeLa cells or infection of H9 and Jurkat cells by HIV-1 increased HRES-1/Rab4 protein levels. Overexpression of HRES-1/Rab4 in Jurkat cells abrogated HIV infection, gag p24 production, and apoptosis, whereas dominant-negative HRES-1/Rab4(S27N) had the opposite effects. HRES-1/Rab4 inhibited surface expression of CD4 and targeted it for lysosomal degradation. HRES-1/Rab4(S27N) enhanced surface expression, recycling, and total cellular CD4 content. Infection by HIV elicited a coordinate down-regulation of CD4 and up-regulation of HRES-1/Rab4 in PBL. Moreover, overexpression of HRES-1/Rab4 reduced CD4 expression on peripheral blood CD4+ T cells. Stimulation by HIV-1 of HRES-1/Rab4 expression and its regulation of CD4 recycling reveal novel coordinate interactions between an infectious retrovirus and the human genome.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34574-91
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16935861-Antigens, CD, pubmed-meshheading:16935861-Antigens, CD4, pubmed-meshheading:16935861-Apoptosis, pubmed-meshheading:16935861-Base Sequence, pubmed-meshheading:16935861-CD4-Positive T-Lymphocytes, pubmed-meshheading:16935861-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:16935861-Dependovirus, pubmed-meshheading:16935861-Disease Susceptibility, pubmed-meshheading:16935861-Exons, pubmed-meshheading:16935861-Flow Cytometry, pubmed-meshheading:16935861-Gene Expression Regulation, Viral, pubmed-meshheading:16935861-Gene Products, tat, pubmed-meshheading:16935861-Genes, Dominant, pubmed-meshheading:16935861-HIV Core Protein p24, pubmed-meshheading:16935861-HIV Infections, pubmed-meshheading:16935861-HIV Long Terminal Repeat, pubmed-meshheading:16935861-HIV-1, pubmed-meshheading:16935861-HeLa Cells, pubmed-meshheading:16935861-Humans, pubmed-meshheading:16935861-Introns, pubmed-meshheading:16935861-Jurkat Cells, pubmed-meshheading:16935861-Lysosomes, pubmed-meshheading:16935861-Molecular Sequence Data, pubmed-meshheading:16935861-Mutagenesis, Site-Directed, pubmed-meshheading:16935861-Mutation, pubmed-meshheading:16935861-Receptors, Transferrin, pubmed-meshheading:16935861-Recombinant Fusion Proteins, pubmed-meshheading:16935861-Sequence Homology, Nucleic Acid, pubmed-meshheading:16935861-Transfection, pubmed-meshheading:16935861-rab4 GTP-Binding Proteins, pubmed-meshheading:16935861-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2006
pubmed:articleTitle
Regulation of CD4 expression via recycling by HRES-1/RAB4 controls susceptibility to HIV infection.
pubmed:affiliation
Department of Medicine, State University of New York, College of Medicine, Syracuse, New York 13210, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural