CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity
- Center for Virology, Burnet Institute, Melbourne, Victoria (Australia)
- Center for Immunology, Burnet Institute, Melbourne, Victoria (Australia)
- Department of Medicine, Monash University, Melbourne, Victoria (Australia)
- Westmead Millennium Institute, Westmead, New South Wales (Australia)
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.
- OSTI ID:
- 21486919
- Journal Information:
- Virology, Vol. 410, Issue 2; Other Information: DOI: 10.1016/j.virol.2010.12.010; PII: S0042-6822(10)00754-3; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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