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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 resistance to neutralization of human immunodeficiency virus type 1 (HIV-1). We find that the presence or absence of this V3 glycan on clade A and B viruses accorded various degrees of susceptibility to neutralization by antibodies to the CD4 binding site, CD4-induced epitopes, and chemokine receptors. Our data suggest that this carbohydrate moiety on gp120 blocks access to the binding site for CD4 and modulates the chemokine receptor binding site of phenotypically diverse clade A and clade B isolates. Its presence also contributes to the masking of CD4-induced epitopes on clade B envelopes. These findings reveal a common mechanism by which diverse HIV-1 isolates escape immune recognition. Furthermore, the observation that conserved functional epitopes of HIV-1 are more exposed on V3 glycan-deficient envelope glycoproteins provides a basis for exploring the use of these envelopes as vaccine components.

* Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, 7th Floor, 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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