Linked Life Data

16365153

Source:http://linkedlifedata.com/resource/pubmed/id/16365153

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-3-1
pubmed:abstractText
The human immunodeficiency virus type 1 (HIV-1) pathogenicity factor Nef increases viral replication in vivo. In immortalized cell lines, Nef affects the cell surface levels of multiple receptors and signal transduction pathways. Resting CD4+ T lymphocytes are important targets for HIV-1 infection in vivo-they actively transcribe and express HIV-1 genes and contribute to the local viral burden and long-lived viral reservoirs in patients undergoing antiretroviral therapy. In vitro, this primary cell type has, however, thus far been highly refractory to experimental manipulation, and the biological activities exerted by HIV-1 Nef in these cells are largely unknown. Using nucleofection for gene delivery, we find that Nef induces a drastic and moderate down-regulation of CD4 and major histocompatibility complex type 1 (MHC-I), respectively, but does not alter surface levels of other receptors, the down-modulation of which has been reported in cell line studies. In contrast, Nef markedly up-regulated cell surface levels of the MHC-II invariant chain CD74. The effect of Nef on these three surface receptors was also detected upon HIV-1 infection of activated primary CD4+ T lymphocytes. Nef expression alone was insufficient to activate resting CD4+ T lymphocytes, but Nef modestly enhanced the responsiveness of cells to exogenous T cell activation. Consistent with such a signal transduction activity, a subpopulation of Nef localized to lipid raft clusters at the plasma membrane. This study establishes the analysis of Nef functions in these primary HIV target cells. Our data support the involvement of modulation of a defined set of cell surface receptors and sensitization to activation rather than an autonomous activation function in the role of Nef in HIV-1 pathogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0741-5400
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
616-27
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16365153-Antigens, CD4, pubmed-meshheading:16365153-Antigens, Differentiation, B-Lymphocyte, pubmed-meshheading:16365153-CD4-Positive T-Lymphocytes, pubmed-meshheading:16365153-Cells, Cultured, pubmed-meshheading:16365153-Down-Regulation, pubmed-meshheading:16365153-Gene Products, nef, pubmed-meshheading:16365153-HIV-1, pubmed-meshheading:16365153-Histocompatibility Antigens Class I, pubmed-meshheading:16365153-Histocompatibility Antigens Class II, pubmed-meshheading:16365153-Humans, pubmed-meshheading:16365153-Immunologic Factors, pubmed-meshheading:16365153-Lymphocyte Activation, pubmed-meshheading:16365153-Membrane Microdomains, pubmed-meshheading:16365153-Receptors, Cell Surface, pubmed-meshheading:16365153-Signal Transduction, pubmed-meshheading:16365153-Transfection, pubmed-meshheading:16365153-Up-Regulation, pubmed-meshheading:16365153-Virus Replication, pubmed-meshheading:16365153-nef Gene Products, Human Immunodeficiency Virus
pubmed:year
2006
pubmed:articleTitle
Modulation of specific surface receptors and activation sensitization in primary resting CD4+ T lymphocytes by the Nef protein of HIV-1.
pubmed:affiliation
Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't