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Glycodelins
GdA and GdS Modified by 3-Hydroxyphthalic Anhydride Inhibit gp120-CD4 Binding
and HIV-1 Infection In Vitro |
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Markku SeppAdalAda,
Shibo Jiang, Nathan Strick, Kang Lin, Yun-Yao Li, Hannu Koistinen, Riitta
Koistinen, and A. Robert Neurath |
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Department
of Obstetrics and Gynecology (MS, HK, RK), Helsinki University Central Hospital,
Helsinki, Finland, and Laboratory of Biochemical Virology (SJ, NS, KL, Y-YL,
ARN), Lindsay F. Kimball Research Institute of the New York Blood Center,
New York, New York |
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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. |
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