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M94A0625.TXT
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1994-10-21
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Document 0625
DOCN M94A0625
TI HIV-1 auxiliary protein Nef down-regulates expression of cellular
receptors and factors involved in signalling.
DT 9412
AU Greenway A; Allen K; McPhee D; AIDS Cellular Biology Unit, Macfarlane
Burnet Centre, NCHVR,; Melbourne, Victoria, Australia.
SO Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:71 (abstract no. SB2).
Unique Identifier : AIDSLINE ASHM5/94349030
AB The function of HIV-1 Nef protein, although poorly understood, has been
implicated in the progression of HIV infection to AIDS. To address the
effect of Nef on cellular activity, Nef protein was introduced into
cells by a sophisticated electroporation technique. Electroporation of
HIV-1 Nef reduced the expression of cell surface CD4 by 30-50%, as
measured by flow cytometry, on phytohemagglutinin (PHA)-activated
peripheral blood mononuclear cells (PBMC) as well as on a variety of
CD4+ T-cell lines (MT-2. CEM and Jurkat). Reduction in surface CD4 was
observed in all cells of the CD4+ T-cell lines but only in the CD4+
cells of the mixed PBMC population. Electroporation of Nef into MT-2
cells and PHA-activated PBMC also reduced the expression of CD25 to
background levels. Other cell surface antigens such as CD2, CD7 or
transferrin receptor were not affected by HIV-1 Nef. Levels of the
proto-oncogene c-myb and phosphorylation of tyrosine kinase p56lck were
also reduced in Nef-treated T-cell lines and PBMC. Thus, Nef has a
significant effect on important host cell receptors and signalling
pathways. Current investigations will delineate whether the down
regulatory effect by Nef is a transcriptional or post-transcriptional
event.
DE Acquired Immunodeficiency Syndrome/*MICROBIOLOGY Cell Line
Down-Regulation (Physiology)/GENETICS Gene Expression Regulation,
Viral/PHYSIOLOGY Genes, nef/*GENETICS Human HIV
Infections/*MICROBIOLOGY HIV-1/*GENETICS/PATHOGENICITY
Monocytes/MICROBIOLOGY Receptors, HIV/*GENETICS Signal
Transduction/*GENETICS Transcription, Genetic/GENETICS T4
Lymphocytes/MICROBIOLOGY Virus Integration/*GENETICS Virus
Replication/*GENETICS MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).