Linked Life Data

8409933

Source:http://linkedlifedata.com/resource/pubmed/id/8409933

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1993-11-16
pubmed:abstractText
We investigated endoproteolytic processing of the human immunodeficiency virus (HIV) envelope glycoprotein precursor, gp160, as well as envelope-mediated membrane fusion in the presence of CD4 molecules that were either partially or fully retained in the endoplasmic reticulum (ER). Pulse-chase analyses revealed that gp160 formed complexes with CD4 molecules, and gp160 in the complex was endoproteolytically cleaved to gp120 and gp41 in the secretory pathway. The gp120/gp41 complex thus generated was properly targeted to the plasma membrane in cells expressing gp160 and wild-type CD4 or mutant CD4 molecules that were partially retained in the ER. Additionally, membrane fusion (syncytium) assays were performed to monitor the presence or absence of gp120/gp41 complexes at the cell surface of cotransfected cells and demonstrated that the HIV-1 envelope glycoprotein-mediated membrane fusion was appreciably reduced in the presence of wild-type CD4 or either one of the mutant CD4 molecules. Reduction in the formation of syncytia appears to be due predominantly to saturation of the CD4 binding site on the gp120/gp41 complex at the cell surface of cotransfected cells, but partial retention of the complex in the ER could also partly account for the reduction. However, the intracellular gp120/gp41 complex generated in cells expressing gp160 and CD4 mutant having the transmembrane ER retention signal (KKTC) was completely retained in the ER and hence could not participate in membrane fusion events at the plasma membrane. Taken together, these data suggest that the endoproteolytic cleavage of gp160 occurs in the ER or cis-Golgi network, and ER retention strategies can potentially be used in preventing the spread of HIV-1 infection in permissive cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1317
pubmed:author
pubmed:issnType
Print
pubmed:volume
74 ( Pt 10)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2085-97
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8409933-Amino Acid Sequence, pubmed-meshheading:8409933-Antigens, CD4, pubmed-meshheading:8409933-Base Sequence, pubmed-meshheading:8409933-Biological Transport, pubmed-meshheading:8409933-Cell Membrane, pubmed-meshheading:8409933-Endoplasmic Reticulum, pubmed-meshheading:8409933-Gene Products, env, pubmed-meshheading:8409933-Giant Cells, pubmed-meshheading:8409933-HIV Envelope Protein gp120, pubmed-meshheading:8409933-HIV Envelope Protein gp160, pubmed-meshheading:8409933-HIV Envelope Protein gp41, pubmed-meshheading:8409933-HIV-1, pubmed-meshheading:8409933-HeLa Cells, pubmed-meshheading:8409933-Humans, pubmed-meshheading:8409933-Molecular Sequence Data, pubmed-meshheading:8409933-Mutation, pubmed-meshheading:8409933-Protein Precursors, pubmed-meshheading:8409933-Viral Fusion Proteins
pubmed:year
1993
pubmed:articleTitle
Analysis of endoproteolytic cleavage and intracellular transport of human immunodeficiency virus type 1 envelope glycoproteins using mutant CD4 molecules bearing the transmembrane endoplasmic reticulum retention signal.
pubmed:affiliation
Department of Molecular Biology, Cleveland Clinic Foundation, Ohio 44195.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.