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Journal of Virology, December 1998, p. 10213-10217, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A Conformation-Specific Monoclonal Antibody Reacting with Fusion-Active gp41 from the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein

Shibo Jiang,1,* Kang Lin,1 and Min Lu2

Lindsley F. Kimball Research Institute, New York Blood Center,1 and Department of Biochemistry, Joan and Sanford I. Weill Medical College, Cornell University,2 New York, New York 10021

Received 27 April 1998/Accepted 20 August 1998

The gp41 subunit of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein plays a major role in the membrane fusion step of viral infection. The ectodomain of gp41 contains a six-helix structural domain that likely represents the core of the fusion-active conformation of the molecule. A monoclonal antibody (MAb), designated NC-1, was generated and cloned from a mouse immunized with the model polypeptide N36(L6)C34, which folds into a stable six-helix bundle. NC-1 binds specifically to both the alpha -helical core domain and the oligomeric forms of gp41. This conformation-dependent reactivity is dramatically reduced by point mutations within the N-terminal coiled-coil region of gp41 which impede formation of the gp41 core. NC-1 binds to the surfaces of HIV-1-infected cells only in the presence of soluble CD4. 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.

* Corresponding author. Mailing address: Lindsley F. Kimball Research Institute, New York Blood Center, 310 E. 67th St., New York, NY 10021. Phone: (212) 570-3058. Fax: (212) 570-3299. E-mail: sjiang{at}nybc.org.

Journal of Virology, December 1998, p. 10213-10217, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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