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Published in: BMC Infectious Diseases 1/2002

Open Access 01-12-2002 | Research article

Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

Authors: A Robert Neurath, Nathan Strick, Shibo Jiang, Yun-Yao Li, Asim K Debnath

Published in: BMC Infectious Diseases | Issue 1/2002

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Abstract

Background

Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles.

Methods

Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41.

Results

1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles.

Conclusions

CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection.
Appendix
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Metadata
Title
Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles
Authors
A Robert Neurath
Nathan Strick
Shibo Jiang
Yun-Yao Li
Asim K Debnath
Publication date
01-12-2002
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2002
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-2-6

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