Document 0452
 DOCN  M9440452
 TI    The simian immunodeficiency virus Nef protein promotes degradation of
       CD4 in human T cells.
 DT    9404
 AU    Sanfridson A; Cullen BR; Doyle C; Department of Immunology, Duke
       University Medical Center, Durham,; North Carolina 27710.
 SO    J Biol Chem. 1994 Feb 11;269(6):3917-20. Unique Identifier : AIDSLINE
       MED/94140797
 AB    Expression of the Nef protein encoded by human and simian
       immunodeficiency viruses results in the specific down-regulation of CD4
       from the cell surface in both lymphoid and non-lymphoid cells. In this
       report, we examine the biosynthesis and cell surface expression of CD4
       in the human T cell line, CEM-SS, that has been stably transduced with
       the SIV nef gene. Quantification of CD4 in Nef-expressing cells reveals
       that the steady state level of CD4 is significantly reduced as compared
       to control transductants. The presence of Nef in these cells promotes
       the degradation of newly synthesized CD4 protein. The biosynthesis and
       oligosaccharide processing of CD4 in Nef-expressing T cells appears to
       be normal through the endoplasmic reticulum and Golgi compartments,
       suggesting that the degradation of CD4 is a late event in the
       biosynthetic pathway. Treatment with the lysosomotropic agents
       chloroquine and primaquine prevents the degradation of CD4 in
       Nef-expressing CEM-SS cells, indicating that the degradation of CD4
       likely occurs in an acidic compartment. Thus the reduced cell surface
       expression observed in Nef-expressing CEM-SS cells is the likely
       consequence of a Nef-induced sorting of CD4 into a cellular compartment
       where CD4 is then degraded.
 DE    Antigens, CD4/*METABOLISM  Biological Transport  Cell Compartmentation
       Endoplasmic Reticulum/METABOLISM  Gene Products, nef/*METABOLISM
       Glucosaminidase/METABOLISM  Golgi Apparatus/METABOLISM  Human  In Vitro
       Lysosomes/METABOLISM  Protein Processing, Post-Translational  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  SIV/*METABOLISM
       Transfection  T4 Lymphocytes/METABOLISM/*MICROBIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).