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

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