CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity
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 alterat...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Published: |
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/6288 |
| _version_ | 1848745033227829248 |
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| author | Sterjovski, J. Churchill, M. Roche, M. Ellett, A. Farrugia, W. Wesselingh, S. Cunningham, A. Ramsland, Paul Gorry, P. |
| author_facet | Sterjovski, J. Churchill, M. Roche, M. Ellett, A. Farrugia, W. Wesselingh, S. Cunningham, A. Ramsland, Paul Gorry, P. |
| author_sort | Sterjovski, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T06:10:55Z |
| format | Journal Article |
| id | curtin-20.500.11937-6288 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:10:55Z |
| publishDate | 2011 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-62882017-09-13T14:41:37Z 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, Paul Gorry, P. 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. 2011 Journal Article http://hdl.handle.net/20.500.11937/6288 10.1016/j.virol.2010.12.010 unknown |
| spellingShingle | Sterjovski, J. Churchill, M. Roche, M. Ellett, A. Farrugia, W. Wesselingh, S. Cunningham, A. Ramsland, Paul Gorry, P. CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity |
| title | CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity |
| title_full | CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity |
| title_fullStr | CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity |
| title_full_unstemmed | CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity |
| title_short | CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity |
| title_sort | cd4-binding site alterations in ccr5-using hiv-1 envelopes influencing gp120-cd4 interactions and fusogenicity |
| url | http://hdl.handle.net/20.500.11937/6288 |