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

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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 membranefusion step of viral infection. The ectodomain of gp41 containsa six-helix structural domain that likely represents the coreof the fusion-active conformation of the molecule. A monoclonalantibody (MAb), designated NC-1, was generated and cloned froma mouse immunized with the model polypeptide N36(L6)C34, whichfolds into a stable six-helix bundle. NC-1 binds specificallyto both the $alpha$ -helical core domain and the oligomeric forms ofgp41. This conformation-dependent reactivity is dramatically reducedby point mutations within the N-terminal coiled-coil region ofgp41 which impede formation of the gp41 core. NC-1 binds to thesurfaces of HIV-1-infected cells only in the presence of solubleCD4. These results indicate that NC-1 is capable of reacting withfusion-active gp41 in a conformation-specific manner and can beused as a valuable biological reagent for studying the receptor-inducedconformational changes in gp41 required for membrane fusion andHIV-1infection.

^* Corresponding author. Mailing address: Lindsley F. Kimball Research Institute, New York Blood Center, 310 E. 67th St., NewYork, 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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