       Document 0830
 DOCN  M9460830
 TI    Association of p56lck with the cytoplasmic domain of CD4 modulates HIV-1
       expression.
 DT    9404
 AU    Tremblay M; Meloche S; Gratton S; Wainberg MA; Sekaly RP; Departement de
       Microbiologie, Universite Laval, Ste-Foy,; Quebec, Canada.
 SO    EMBO J. 1994 Feb 15;13(4):774-83. Unique Identifier : AIDSLINE
       MED/94155841
 AB    To investigate the role played by the cytoplasmic domain of the CD4
       glycoprotein in the process of HIV infection, we have transfected two
       CD4-negative human T cell lines with cDNAs encoding the full-length CD4
       and a truncated form of the molecule, lacking most of the cytoplasmic
       domain. Levels of viral replication were significantly higher in cells
       carrying the truncated version of CD4, in comparison with cells
       expressing the full-length CD4, as measured by the percentage of cells
       expressing viral p24 protein and the number of infectious particles
       released into culture supernatants. The extent of viral entry and
       reverse transcription was similar in each case, as monitored by an
       enzymatic test and quantitative PCR. Quantitative differences at RNA and
       protein levels were responsible for changes in viral production. To
       further characterize the mechanisms responsible for decreased rates of
       HIV replication in CD4-expressing cells we have treated the different
       cell lines, very early after HIV infection, with azidothymidine and
       soluble CD4, two antiviral agents that inhibit replication of HIV at
       different stages in the virus replicative cycle. Results from these
       experiments indicate that a cellular signal is mediated by the CD4
       molecule, which negatively regulates the expression of viral DNA already
       present in such cells. This signal would be initiated following
       oligomerization of the CD4 molecule by the virus itself. Results from
       experiments with a CD4 construct containing mutations of the cysteine
       residues which are responsible for association of CD4 with p56lck
       demonstrate that p56lck is implicated in the transduction of the signal
       negatively regulating HIV replication.
 DE    Antigens, CD4/GENETICS/IMMUNOLOGY/*METABOLISM  Base Sequence
       Cytoplasm/METABOLISM  Human  HIV-1/*PHYSIOLOGY  Molecular Sequence Data
       Protein-Tyrosine Kinase/*METABOLISM  RNA, Viral/METABOLISM  Signal
       Transduction  Support, Non-U.S. Gov't
       T-Lymphocytes/IMMUNOLOGY/MICROBIOLOGY  Tumor Cells, Cultured  Viral
       Proteins/METABOLISM  Virus Integration  Virus Replication  JOURNAL
       ARTICLE

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

