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dc.contributor.authorSterjovski, J.
dc.contributor.authorChurchill, M.
dc.contributor.authorRoche, M.
dc.contributor.authorEllett, A.
dc.contributor.authorFarrugia, W.
dc.contributor.authorWesselingh, S.
dc.contributor.authorCunningham, A.
dc.contributor.authorRamsland, Paul
dc.contributor.authorGorry, P.
dc.identifier.citationSterjovski, J. and Churchill, M. and Roche, M. and Ellett, A. and Farrugia, W. and Wesselingh, S. and Cunningham, A. et al. 2011. CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity. Virology. 410 (2): pp. 418-428.

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.

dc.titleCD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity
dc.typeJournal Article
curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusOpen access via publisher

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