The N-Terminal V3 Loop Glycan Modulates the Interaction of Clade A and B Human Immunodeficiency Virus Type 1 Envelopes with CD4 and Chemokine Receptors

doi:10.1128/JVI.74.23.11008-11016.2000

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Journal of Virology, December 2000, p. 11008-11016, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The N-Terminal V3 Loop Glycan Modulates the Interaction of Clade A and B Human Immunodeficiency Virus Type 1 Envelopes with CD4 and Chemokine Receptors

Susan E. Malenbaum,¹ David Yang,¹ Lisa Cavacini,² Marshall Posner,² James Robinson,³ and Cecilia Cheng-Mayer¹^,^*

Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016¹; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215²; and Department of Pediatrics, Tulane University Medical Center, New Orleans, Louisiana 70112³

Received 11 May 2000/Accepted 1 September 2000

We investigated the underlying mechanism by which the highly conserved N-terminal V3 loop glycan of gp120 conferred resistanceto neutralization of human immunodeficiency virus type 1 (HIV-1).We find that the presence or absence of this V3 glycan on cladeA and B viruses accorded various degrees of susceptibility toneutralization by antibodies to the CD4 binding site, CD4-inducedepitopes, and chemokine receptors. Our data suggest that thiscarbohydrate moiety on gp120 blocks access to the binding sitefor CD4 and modulates the chemokine receptor binding site of phenotypicallydiverse clade A and clade B isolates. Its presence also contributesto the masking of CD4-induced epitopes on clade B envelopes. Thesefindings reveal a common mechanism by which diverse HIV-1 isolatesescape immune recognition. Furthermore, the observation that conservedfunctional epitopes of HIV-1 are more exposed on V3 glycan-deficientenvelope glycoproteins provides a basis for exploring the useof these envelopes as vaccinecomponents.

^* Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, 7thFloor, New York, NY 10016. Phone: (212) 448-5000. Fax: (212) 448-5159.E-mail: cmayer{at}adarc.org.

Journal of Virology, December 2000, p. 11008-11016, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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