CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity

Sterjovski, J, Churchill, M, Roche, M, Ellett, A, Farrugia, W, Wesselingh, S, Cunningham, A, Ramsland, P and Gorry, P 2011, 'CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity', Virology, vol. 410, pp. 418-428.


Document type: Journal Article
Collection: Journal Articles

Title CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity
Author(s) Sterjovski, J
Churchill, M
Roche, M
Ellett, A
Farrugia, W
Wesselingh, S
Cunningham, A
Ramsland, P
Gorry, P
Year 2011
Journal name Virology
Volume number 410
Start page 418
End page 428
Total pages 11
Publisher Academic Press
Abstract CD4-binding site (CD4bs) alterations in gp120 contribute to different pathophysiological phenotypes of CCR5- using (R5) HIV-1 strains, but the potential structural basis is unknown. Here, we characterized functionally diverse R5 envelope (Env) clones (n= 16) to elucidate potential structural alterations within the gp120 CD4bs that influence Env function. Initially, we showed that the magnitude of gp120-CD4-binding correlates with increased fusogenicity and reduced CD4 dependence. Analysis of three-dimensional gp120 structural models revealed two CD4bs variants, D279 and N362, that were associated with reduced CD4 dependence. Further structural analysis showed that a wider aperture of the predicted CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop, was associated with amino acid alterations within V5 and correlated with increased gp120-CD4 binding and increased fusogenicity. Our results provide evidence that the gp120 V5 loop may alter CD4bs conformation and contribute to increased gp120-CD4 interactions and Env fusogenicity
Subject Infectious Diseases
Clinical Sciences not elsewhere classified
Keyword(s) HIV-1
CD4
CD4bs
gp120
Fusogenicity
DOI - identifier 10.1016/j.virol.2010.12.010
Copyright notice © 2010 Elsevier Inc. All rights reserved.
ISSN 0042-6822
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