Document 0286
 DOCN  M9460286
 TI    HIV-1 Nef activity in murine T cells. CD4 modulation and positive
       enhancement.
 DT    9408
 AU    Rhee SS; Marsh JW; Laboratory of Molecular Biology, National Institute
       of Mental; Health, Bethesda, MD 20892.
 SO    J Immunol. 1994 May 15;152(10):5128-34. Unique Identifier : AIDSLINE
       MED/94230994
 AB    Immediately after infection of the targeted cell by HIV-1, proviral gene
       expression is limited to the three regulatory proteins, Tat, Rev, and
       Nef, with the nef transcript representing nearly 80% of total
       expression. Additionally, simian immunodeficiency virus Nef has been
       shown to be essential for high in vivo titer and the development of
       immunodeficiency. Recent findings demonstrate that the negative effects
       of Nef expression, as first defined in transformed T cell lines, are not
       present when Nef is expressed in primary human T cells or in T cells
       from transgenic mice, in which one sees moderate positive enhancements
       of HIV replication and the T cell activation process, respectively. We
       find that Nef expression in an Ag-specific murine T cell hybridoma
       results in both the down-modulation of CD4, as seen in primary cells and
       human T cell lines, and a positive enhancement of the TCR response to
       stimuli. Examination of a CD4- cell demonstrated that the positive
       enhancement is independent of CD4 expression or modulation. CD4
       down-modulation is shown to be caused by a post-Golgi, acid-dependent
       process, which dramatically decreases the lifespan of the CD4 molecule.
       The TCR, Thy Ag, and CD45 remained unchanged in their surface
       expression. These findings suggest that Nef alters the normal routing
       and residencies of the CD4 molecule and that the positive effect of Nef
       on T cell activation is independent of this modulation.
 DE    Animal  Antigens, CD4/*ANALYSIS  Cell Line  Down-Regulation (Physiology)
       Gene Products, nef/*PHYSIOLOGY  HIV-1/*PATHOGENICITY
       Interleukin-2/BIOSYNTHESIS  Lymphocyte Transformation  Mice  Receptors,
       Antigen, T-Cell/PHYSIOLOGY  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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