Linked Life Data

16684552

Source:http://linkedlifedata.com/resource/pubmed/id/16684552

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-7-31
pubmed:abstractText
Nef is an important pathogenesis factor of HIV-1 with a multitude of effector functions. We have designed a broad panel of isogenic viruses encoding defined mutants of HIV-1(SF2) Nef and analyzed their biological activity in the context of productive HIV-1 infection. Analysis of subcellular localization, virion incorporation, downregulation of cell surface CD4 and MHC-I, enhancement of virion infectivity and facilitation of HIV replication in primary human T lymphocytes mostly confirmed the mapping of Nef determinants previously reported upon isolated expression of Nef. However, reduced activity in downregulation of CD4, infectivity enhancement and virion incorporation of a Nef variant (Delta12-39) lacking an amphipatic helix required for binding of a cellular kinase complex and the association of Nef with MHC-I/AP-1 suggested a novel role of this N-terminal motif. The SH3 binding motif of Nef was partially required for infectivity enhancement and replication but not for receptor downmodulation. In contrast to previous results obtained using other Nef alleles, non-myristoylated SF2-Nef was only partly defective when expressed during HIV infection and was present in HIV-1 particles. Importantly, incorporation of Nef into HIV-1 virions was not required for any of the tested Nef activities. Altogether, this study provides a broad characterization and mapping of multiple Nef activities in HIV-infected cells. The results emphasize that multiple activities govern Nef's effects on HIV replication and argue against a role of virion incorporation for Nef's activity as pathogenicity factor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
351
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
322-39
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Functional characterization of HIV-1 Nef mutants in the context of viral infection.
pubmed:affiliation
Department of Virology, University of Heidelberg, INF 324, D-69120 Heidelberg, Germany. oliver_fackler@med.uni-heidelberg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't