GLYCODELINS GDA AND GDS MODIFIED BY 3-HYDROXYPHTHALIC ANHYDRIDE INHIBIT GP120-CD4 BINDING AND HIV-1 INFECTION IN-VITRO

Bovine beta-lactoglobulin chemically modified with 3-hydroxyphthalic a nhydride (3HP) was recently shown, at nanomolar concentrations, to blo ck the binding site on CD4 for the HIV surface glycoprotein (gp120), p otentially inhibiting HIV transmission. Human glycodelin has sequence homology with bovine beta-lactoglobulin and appears as different glyco forms in endometrium (GdA) and seminal plasma (GdS). We studied the an ti-HIV effects of chemically modified GdA and GdS on both the infectio n of MT-2 cells by HIV-1(IIB), and the infection of peripheral blood m ononuclear cells by the primary HIV isolate THA/93/051 belonging to su btype E. Whereas the native proteins were inactive when tested at phys iologic concentrations, nanomolar concentrations of either 3HP-GdA or 3HP-GdS inhibited the production of HIV nucleocapsid p24, cytopathic e ffects of HIV-1(IIIB), and infection of peripheral brood mononuclear c ells by the primary HIV isolate THA/93/051. Moreover, both modified pr oteins inhibited gp120-GD4 binding, 3HP-GdS being more potent than 3HP -GdA (p = 0.0042). Because GdA and GdS have the same major protein cor e, the observed difference in gp120-CD4 binding must depend on the spe cific glycoform. In view of the previously reported contraceptive acti vity of GdA, the observed anti-HIV activity induced by its chemical mo dification should be of special interest in the development of antivir al strategies that may also have contraceptive effects.