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.
Lemasson
I
I
Laboratory of Immunology for Retroviral Infections, INSERM U249, Institute of Biology, Montpellier, France.
Briant
L
L
Hague
B
B
Coudronnière
N
N
Heron
L
L
David
C
C
Rebouissou
C
C
Kindt
T
T
Devaux
C
C
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