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 anhydride (3HP) was recently shown, at nanomolar concentrations, to block the binding site on CD4 for the HIV surface glycoprotein (gp120), potentially inhibiting HIV transmission. Human glycodelin has sequence homology with bovine beta-lactoglobulin and appears as different glycoforms in endometrium (GdA) and seminal plasma (GdS). We studied the anti-HIV effects of chemically modified GdA and GdS on both the infection of MT-2 cells by HIV-1IIIB, and the infection of peripheral blood mononuclear cells by the primary HIV isolate THA/93/051 belonging to subtype E. Whereas the native proteins were inactive when tested at physiologic concentrations, nanomolar concentrations of either 3HP-GdA or 3HP-GdS inhibited the production of HIV nucleocapsid p24, cytopathic effects of HIV-1IIIB, and infection of peripheral blood mononuclear cells by the primary HIV isolate THA/93/051. Moreover, both modified proteins inhibited gp120-CD4 binding, 3HP-GdS being more potent than 3HP-GdA (p = 0.0042). Because GdA and GdS have the same major protein core, the observed difference in gp120-CD4 binding must depend on the specific glycoform. In view of the previously reported contraceptive activity of GdA, the observed anti-HIV activity induced by its chemical modification should be of special interest in the development of antiviral strategies that may also have contraceptive effects.
Seppälä
M
M
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Jiang
S
S
Strick
N
N
Lin
K
K
Li
Y Y
YY
Koistinen
H
H
Koistinen
R
R
Neurath
A R
AR
D019380:Anti-HIV Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D000071816:Glycodelin; D006023:Glycoproteins / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D010795:Phthalic Acids / Q000494:pharmacology; D011257:Pregnancy Proteins / Q000494:pharmacology*
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D000071816:Glycodelin; D006023:Glycoproteins; D015699:HIV Envelope Protein gp120; C045246:PAEP protein, human; D010795:Phthalic Acids; D011257:Pregnancy Proteins