       Document 0396
 DOCN  M9620396
 TI    The cytoplasmic tail of CD4 is required for inhibition of human
       immunodeficiency virus type 1 replication by antibodies that bind to the
       immunoglobulin CDR3-like region in domain 1 of CD4.
 DT    9602
 AU    Benkirane M; Schmid-Antomarchi H; Littman DR; Hirn M; Rossi B; Devaux C;
       Laboratoire d'Immunologie des Infections Retrovirales, Centre; National
       de la Recherche Scientifique UPR9008, Institute de; Biologie,
       Montpellier, France.
 SO    J Virol. 1995 Nov;69(11):6904-10. Unique Identifier : AIDSLINE
       MED/96013790
 AB    Monoclonal antibodies (MAb) directed against the immunoglobulin
       complementary determining region 3 (CDR3)-like region of the CD4
       molecule inhibit human immunodeficiency virus type 1 (HIV-1)
       transcription. We report here data showing that the cytoplasmic tail of
       CD4 is required for such inhibition to be achieved. To this aim, we
       studied the effect of MAb 13B8-2 treatment on (i) HIV-1 production in
       A2.01 cells, which express different forms of the CD4 gene, (ii)
       Tat-induced HIV-1 promoter activation, and (iii) mitogen-activated
       protein kinase (MAPK) activation, which is induced in CD4-positive cells
       by HIV-1 cross-linking of CD4. Inhibition of HIV production by 13B8-2
       MAb treatment was consistently observed in cells expressing wild-type
       CD4 and cells expressing a hybrid CD4-CD8 molecule (amino acids 1 to 177
       of CD4 fused to the hinge, transmembrane, and cytoplasmic domains of
       CD8). However, no delay in HIV-1 production was observed in cells
       expressing a truncated CD4 which lacks the cytoplasmic domain (CD4.401).
       Chloramphenicol acetyltransferase assays demonstrated that Tat-dependent
       activation of the HIV-1 long terminal repeat promoter was inhibited by
       MAb 13B8-2 in A2.01/CD4 and A2.01/CD4-CD8 but not in A2.01/CD4.401
       cells. Finally, we found that MAb 13B8-2 treatment inhibited the
       activation of MAPK induced in A2.01/CD4 and A2.01/CD4-CD8 following
       cross-linking of CD4 by HIV-1.
 DE    Antibodies, Monoclonal/*PHARMACOLOGY  Antigens,
       CD/BIOSYNTHESIS/*PHYSIOLOGY  Antigens, CD4/BIOSYNTHESIS/*PHYSIOLOGY
       Binding Sites, Antibody  Calmodulin-Dependent Protein Kinases/METABOLISM
       Cell Line  Chloramphenicol Acetyltransferase/BIOSYNTHESIS  Clone Cells
       Comparative Study  Flow Cytometry  Human  HIV-1/IMMUNOLOGY/*PHYSIOLOGY
       Kinetics  Receptor-CD3 Complex, Antigen, T-Cell/*PHYSIOLOGY  Recombinant
       Proteins/BIOSYNTHESIS  Support, Non-U.S. Gov't  T-Lymphocytes
       Transfection  *Virus Replication  JOURNAL ARTICLE

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

