Ig CDR3-like region of the CD4 molecule is involved in HIV-induced syncytia formation but not in viral entry.
The HIV1 envelope glycoprotein gp120 binding site has been previously mapped by genetic studies to the CDR2-like region of the first domain of the CD4 molecule. mAb reactive with epitopes linked to this region (e.g., OKT4A) inhibit both HIV entry into CD4-positive cells and syncytia formation. A second area of this domain, the CDR3-like region, has been shown to be involved in gp120-CD4 interactions, but its role remained so far unclear. We show here that a mAb specific for the CDR3-like region of the CD4 receptor, 13B8-2, actually blocks soluble gp120 binding to CD4, inhibits HIV-induced cell-cell fusion, and prevents viral production by infected cells. However, this mAb fails to inhibit the binding of viral particles to cell-surface CD4 and their entry into CD4-positive cells. These results strongly suggest i) that soluble gp120 and virion-anchored gp120 bind CD4 in distinct manners, ii) that gp120-CD4 interactions required for viral entry and syncytia formation are different, and iii) that mAb binding to the CDR3-like region of the first domain of CD4 affects a post-entry step of the HIV replicative cycle.
Corbeau
P
P
CRBM du CNRS, Centre de Tri des Molécules anti-HIV, Institut de Biologie, Montpellier, France.
Benkirane
M
M
Weil
R
R
David
C
C
Emiliani
S
S
Olive
D
D
Mawas
C
C
Serre
A
A
Devaux
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000998:Antiviral Agents / Q000276:immunology; D001483:Base Sequence; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006678:HIV / Q000276:immunology / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000502:physiology*; D008969:Molecular Sequence Data; D014779:Virus Replication / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007135:Immunoglobulin Variable Region