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M94A3330.TXT
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1994-10-25
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Document 3330
DOCN M94A3330
TI Gp120 induces CD4-association with membrane component(s) and
susceptibility to PMA-induced co-modulation.
DT 9412
AU Golding H; Lapham C; CBER, FDA, Bethesda, MD 20892.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):100 (abstract no. PA0017). Unique
Identifier : AIDSLINE ICA10/94369245
AB OBJECTIVE: To identify additional membrane components required for HIV-1
entry and envelope mediated fusion (CD4-co-receptor). METHODS: Using
cell lines expressing either tailless CD4 molecules (CD4.401) or
chimeric CD4.CD8 molecules, we found that PMA does not induce
down-modulation of these receptors. Yet PMA treatment dramatically
inhibited HIV-1 env-mediated fusion and infection, due to
down-modulation of a co-receptor expressed by the CD4-bearing cells (H.
Golding et al J. Virol. 1994). In the current study, soluble gp120 was
added to these cell lines at different temperatures followed by 3 hr PMA
treatment. Surface expression of the CD4.401 and CD4.CD8 molecules was
determines by FACS analysis. RESULTS: Incubation of CD4.401-expressing
cells with monomeric soluble gp120 for 1-2 hr at 37 degrees C, resulted
in small (25-35%) down-modulation of the CD4 receptors. However,
subsequent treatment with PMA for 3 hr at 37 degrees C, resulted in
marked (50-70%) down-modulation of the CD4 molecules. The ability of
gp120 to prime cells for CD4-down-modulation was temperature dependent
since it was not seen after incubation at 4 degrees C under maximal
binding conditions. Furthermore, gp120 incubation in the presence of
hypertonic buffer which blocks formation of clathrine coated pits
blocked the subsequent PMA-induced down-modulation. Interestingly, gp120
treatment of the CD4.CD8-expressing cells (which contain two membrane
proximal domains and cytoplasmic tail from CD8), did not result in
significant down-modulation by subsequent PMA treatment. DISCUSSION: Our
data suggest that incubation of cells with gp120 induces conformational
changes in the CD4 receptors resulting in their association with other
surface component(s). These complexes are susceptible to
co-down-modulation via clathrine-coated pits. The membrane proximal
domains of CD4 may be involved in this association.
DE Antigens, CD4/DRUG EFFECTS/GENETICS/*PHYSIOLOGY Antigens,
CD8/GENETICS/PHYSIOLOGY Cell Fusion/PHYSIOLOGY Cell Line Cell
Membrane/DRUG EFFECTS/MICROBIOLOGY/PHYSIOLOGY Coated Pits,
Cell-Membrane/DRUG EFFECTS/MICROBIOLOGY/PHYSIOLOGY Down-Regulation
(Physiology) Human HIV Envelope Protein gp120/*PHYSIOLOGY HIV-1/DRUG
EFFECTS/*PHYSIOLOGY/PATHOGENICITY Recombinant Proteins/GENETICS
Tetradecanoylphorbol Acetate/PHARMACOLOGY MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).