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Journal of Virology, March 2002, p. 2827-2834, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2827-2834.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Antibody-Mediated Enhancement of Human Immunodeficiency Virus Type 1 Infectivity Is Determined by the Structure of gp120 and Depends on Modulation of the gp120-CCR5 Interaction

Christophe Guillon,1,{dagger} Martin Schutten,1 Patrick H. M. Boers,1 Rob A. Gruters,1,2 and Albert D. M. E. Osterhaus1*

Department of Virology, Erasmus University Rotterdam, 3015 GE Rotterdam, The Netherlands ,1 UMR 2142 CNRS/bioMérieux, ENS Lyon, 69364 Lyon, France2

Received 30 May 2001/ Accepted 7 December 2001

In this study, we characterized the viral determinants of coreceptor usage in relation to susceptibility to antibody-mediated neutralization or enhancement of infectivity by using chimeras of three highly related human immunodeficiency virus type 1 (HIV-1) isolates of different phenotypes. We found that the V3 region was the main determinant of antibody-mediated enhancement and coreceptor specificity but that the overall structure of gp120 was also important for these properties. Constructs susceptible to antibody-mediated enhancement preferentially use CCR5 as a coreceptor, in contrast to constructs that were neutralized or not affected. Using monoclonal antibodies directed against CD4 or CCR5, we were able to show that antibody-mediated enhancement was CD4 dependent. Altogether, our results suggest that the modulation of the interaction of gp120 with CCR5 is the mechanism underlying antibody-mediated enhancement of HIV-1 infectivity.

* Corresponding author. Mailing address: Erasmus University Rotterdam, Department of Virology, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. Phone: (31) 10 408 8066. Fax: (31) 10 408 9485. E-mail: osterhaus{at}viro.fgg.eur.nl.

{dagger} Present address: UMR 2142 CNRS/bioMérieux, Tour CERVI, 69007 Lyon, France.

Journal of Virology, March 2002, p. 2827-2834, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2827-2834.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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Copyright © 2002 by the American Society for Microbiology. All rights reserved.