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Journal of Virology, June 2001, p. 5593-5603, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5593-5603.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antigenic Variation within the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120: Effects on Chemokine Receptor Utilization

Anthea L. Hammond,1,* Julie Lewis,1 Jackie May,2 Jan Albert,3 Peter Balfe,2 and Jane A. McKeating1,dagger

School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 2AJ,1 and Department of Virology, Windeyer Institute, Royal Free and University College Medical School, London W1P 6DB,2 United Kingdom, and Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, Sweden3

Received 11 December 2000/Accepted 16 March 2001

To assess the antigenicity of envelope glycoproteins derived from primary human immunodeficiency virus type 1 populations, their interactions with the receptor CD4, and their coreceptor usage, we have cloned and expressed multiple gp120 proteins from a number of primary virus isolates. Characterization of these proteins showed a high degree of antigenic polymorphism both within the CD4 binding site and in defined neutralization epitopes, which may partially account for the general resistance of primary isolates to neutralizing agents. Furthermore, chimeric viruses expressing gp120 proteins with reduced CD4 binding abilities are viable, suggesting that primary viruses may require a less avid interaction with the receptor CD4 to initiate infection than do their laboratory-adapted counterparts. The coreceptor usage of chimeric viruses was related to the ability of the virus to bind CD4, with reduced CD4 binding correlating with preferential usage of CXCR4. Changes in coreceptor usage mapped to sequence changes in the C2 and V4 regions, with no changes seen in the V3 region.

* Corresponding author. Present address: Molecular Medicine Program, Guggenheim 1838, Mayo Foundation, 200 1st St. SW, Rochester, MN 55905. Fax: (507) 284-8388. E-mail: murphy.anthea{at}mayo.edu.

dagger Present address: Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10021.

Journal of Virology, June 2001, p. 5593-5603, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5593-5603.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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