Ig CDR3-like region of the CD4 molecule is involved in HIV-induced syncytia formation but not in viral entry
- CRBM du CNRS, Montpellier (France)
- Unite INSERM 119, Marseille (France)
- Hopital Lapeyronnie, Montpellier (France)
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. The authors 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 (1) that soluble gp120 and virion-anchored gp120 bind CD4 in distinct manners, (2) that gp120-CD4 interactions required for viral entry and syncytia formation are different, and (3) that mAb binding to the CDR3-like region of the first domain of CD4 affects a post-entry step of the HIV replicative cycle. 55 refs., 7 figs., 2 tabs.
- OSTI ID:
- 6792371
- Journal Information:
- Journal of Immunology; (United States), Journal Name: Journal of Immunology; (United States) Vol. 150:1; ISSN 0022-1767; ISSN JOIMA3
- Country of Publication:
- United States
- Language:
- English
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