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Journal of Virology, November 1998, p. 8943-8951, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Development of a Neutralizing Antibody Response during Acute Primary Human Immunodeficiency Virus Type 1 Infection and the Emergence of Antigenic Variants

J. Lewis,1 P. Balfe,2,* C. Arnold,3 S. Kaye,2 R. S. Tedder,2 and J. A. McKeating1

School of Animal and Microbial Sciences, University of Reading, Reading RG6 2AJ,1 Department of Virology, The Windeyer Institute of Medical Sciences, UCLMS, London W1P 6DB,2 and Virus Reference Laboratory, CPHL, Colindale, London NW9 5HT,3 United Kingdom

Received 8 May 1998/Accepted 4 August 1998

We monitored the primary humoral response to human immunodeficiency virus type 1 infection and showed that, in addition to antibodies to p24 and gp41, antigens which form the basis of most diagnostic assays, the response included a significant antibody response directed to the gp120 region of the infecting viral quasispecies. When tested in a recombinant virus neutralization assay, these antibodies were capable of inhibiting viral growth. We found the primary viral quasispecies to solely utilize the CCR-5 chemokine receptor; however, recombinant viruses differed in their cytopathology and in their sensitivity to beta -chemokine inhibition of viral growth. Sequence analysis of the gp120 open reading frames showed that amino acid changes in the C1 (Dright-arrowG at position 62) and C4 (Vright-arrowA at position 430) regions accounted for the phenotypic differences. These data demonstrate that early in infection, polymorphism exists in envelope glycoprotein coreceptor interactions and imply that therapeutic strategies targeted at this step in the viral life cycle may lead to rapid resistance.

* Corresponding author. Mailing address: Department of Virology, The Windeyer Institute of Medical Sciences, UCLMS, 46 Cleveland St., London W1P 6DB, United Kingdom. Phone: 44 171 504 9490. Fax: 44 171 580 5896. E-mail: p.balfe{at}ucl.ac.uk.

Journal of Virology, November 1998, p. 8943-8951, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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