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Journal of Virology, September 1998, p. 7280-7288, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Dissociation of the CD4 and CXCR4 Binding Properties of Human Immunodeficiency Virus Type 1 gp120 by Deletion of the First Putative Alpha-Helical Conserved Structure

Dorothée Missé,1,2 Martine Cerutti,2 Isabelle Schmidt,2 Aline Jansen,1 Gérard Devauchelle,2 Franz Jansen,1 and Francisco Veas1,2,*

Laboratoire d'Immunologie Rétrovirale, Institut Français de Recherches pour le Développement en Coopération, 34032 Montpellier,1 and Centre National de la Recherche Scientifique, URA 2209, INRA, 30380 Saint Christol lez Alès,2 France

Received 12 March 1998/Accepted 28 May 1998

To evaluate conserved structures of the surface gp120 subunit (SU) of the human immunodeficiency virus type 1 (HIV-1) envelope in gp120-cell interactions, we designed and produced an HIV-1 IIIB (HXB2R) gp120 carrying a deletion of amino acids E61 to S85. This sequence corresponds to a highly conserved predicted amphipathic alpha-helical structure located in the gp120 C1 region. The resultant soluble mutant with a deleted alpha helix 1 (gp120 Delta alpha HX1) exhibited a strong interaction with CXCR4, although CD4 binding was undetectable. The former interaction was specific since it inhibited the binding of the anti-CXCR4 monoclonal antibody (12G5), as well as SDF1alpha , the natural ligand of CXCR4. Additionally, the mutant gp120 was able to bind to CXCR4+/CD4- cells but not to CXCR4-/CD4- cells. Although efficiently expressed on cell surface, HIV envelope harboring the deleted gp120 Delta alpha HX1 associated with wild-type transmembrane gp41 was unable to induce cell-to-cell fusion with HeLa CD4+ cells. Nevertheless, the soluble gp120 Delta alpha HX1 efficiently inhibited a single round of HIV-1 LAI infection in HeLa P4 cells, with a 50% inhibitory concentration of 100 nM. Our data demonstrate that interaction with the CXCR4 coreceptor was maintained in a SUgp120 HIV envelope lacking alpha HX1. Moreover, in the absence of CD4 binding, the interaction of gp120 Delta alpha HX1 with CXCR4 was sufficient to inhibit HIV-1 infection.

* Corresponding author. Mailing address: Laboratoire d'Immunologie Rétrovirale, Institut Français de Recherches pour le Développement en Coopération, 911 Av. Agropolis, 34032 Montpellier, France. Phone: 33 4 67 61 64 31. Fax: 33 4 67 52 83 80. E-mail: veas{at}mpl.orstom.fr.

Journal of Virology, September 1998, p. 7280-7288, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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