An antibody that binds domain 1 of CD4 inhibits replication of HIV-1, but not HTLV-I, in a CD4-positive/p56lck-negative HTLV-I-transformed cell line.
mAbs that bind to the Ig CDR3-like region in D1 domain of the CD4 molecule can inhibit the HIV-1 life cycle in CD4-positive T cells and lymphoblastoid cell lines at the stage of transcription. This antiviral effect requires the integrity of the cytoplasmic tail of CD4, which acts as a signal transduction region through its association with protein tyrosine kinases such as p56Ick. Here we investigated the role of p56Ick in the cascade of molecular events that control HIV-1 transcription in cells treated with anti-CD4 mAb directed against the Ig CDR3-like region. The Ig CDR3-like region-specific mAb, 13B8-2, blocked HIV-1 production in CD4-positive/p56Ick-negative HTLV-I-producing MT2 cells superinfected by HIV-1Lai, but had no effect on HTLV-I production, although it did inhibit Tax-induced NF-kappa B translocation. These results raise the possibility that an as yet unidentified tyrosine kinase may be capable of associating with CD4 and mediating intracellular signaling.
Laboratory of Immunology for Retroviral Infections, INSERM U249, Institute of Biology, Montpellier, France.
I
I
Lemasson
L
L
Briant
B
B
Hague
N
N
Coudronnière
L
L
Heron
C
C
David
C
C
Rebouissou
T
T
Kindt
C
C
Devaux
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D002461:Cell Line, Transformed; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D016356:Gene Products, tax / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014779:Virus Replication / Q000187:drug effects*; D001613:beta 2-Microglobulin / Q000276:immunology; D019061:src-Family Kinases / Q000032:analysis / Q000172:deficiency / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015704:CD4 Antigens; D000939:Epitopes; D016356:Gene Products, tax; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D001613:beta 2-Microglobulin; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases