AIDSWEEKLY Plus; Monday, December 7, 1998
Daniel J. DeNoon, Senior Editor
One reason why antibodies fail to neutralize HIV is that a key element in fusion of the virus to target cells - the gp41 transmembrane glycoprotein - remains tucked away like a coiled coil. Events triggered by binding of other HIV envelope elements to the CD4 cell-surface molecule release this spring-like mechanism. Only then does it take on its active conformation and penetrate the cell wall.
Now Shibo Jiang of the New York Blood Center and colleagues have developed NC-1, a monoclonal antibody (MAb) capable of binding to the fusion-active portion of gp41.
"NC-1 binds to the surfaces of HIV-1 infected cells only in the presence of soluble CD4," Jiang et al. reported. "These results indicate that NC-1 is capable of reacting with fusion-active gp41 in a conformation-specific manner and can be used as a valuable biological reagent for studying the receptor-induced conformational changes in gp41 required for membrane fusion and HIV-1 infection."
Jiang et al. announced their findings in the Journal of Virology ("A Conformation-Specific Monoclonal Antibody Reacting with Fusion- Active gp41 from The Human Immunodeficiency Virus Type 1 Envelope Glycoprotein," J Virol, 1998;72(12):10213-7).
The researchers created a six-helix model polypeptide that mimics the core of the fusion-active conformation of gp41. They used this polypeptide to generate mouse antibodies that then were cloned to make NC-1.
The MAb specifically binds not only to the alpha-helical core domain of gp41 but also to the molecule's oligomeric forms.
Interestingly, even high concentrations of NC-1 did not neutralize HIV or block fusion of HIV-infected cells to susceptible uninfected cells. Jiang et al. speculate that either the epitope(s) recognized by NC-1 are not neutralizing epitopes or that these epitopes are buried within the HIV gp120/gp41 complex and are not accessible to antibody.
This work was supported by a National Institutes of Health grant and by the City of New York Council Speaker's Fund for Biomedical Research.
The corresponding author for this study is Shibo Jiang, Lindsley F. Kimball Research Institute, New York Blood Center, 310 E. 67th St., New York, New York 10021. Phone: (212) 570-3085. Fax: (212) 570- 3299. Email: <sjiang@nybc.org>.
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