Exploring the role of the “glycan-shield” of human immunodeficiency virus in susceptibility to, and escape from, broadly neutralising antibodies

dc.contributor.advisorTravers, Simon A.
dc.contributor.authorFerreira, Roux-Cil
dc.date.accessioned2019-05-09T07:28:13Z
dc.date.accessioned2024-05-17T07:57:46Z
dc.date.available2019-05-09T07:28:13Z
dc.date.available2024-05-17T07:57:46Z
dc.date.issued2018
dc.descriptionPhilosophiae Doctor - PhDen_US
dc.description.abstractThe HIV-1 envelope (Env) glycoprotein is the primary target of the humoral immune response and a critical vaccine candidate. However, Env is densely glycosylated and thereby substantially protected from neutralisation. Despite the importance of the HIV- 1 Env glycans, limited computational analyses have been employed to analyse these glycans. Here, the Env glycans of two HIV-1 wild-type subtype C isolates are examined, in detail, using computational approaches. These particular strains were used since in vitro data showed that the removal of a single glycan had a substantially different impact on the neutralisation sensitivity of the two strains. Molecular dynamics simulations, and the subsequent analyses, were carried out on the computationally determined, fully glycosylated, Env structures of these two wild-type strains and their N301A mutant counterparts. Detailed comparison of the molecular dynamics simulations demonstrated that unique glycan dynamics and conformations emerged and that, despite shared HXB2 reference sequence positions, the glycans adopted distinct conformations specific to each wild-type model. Furthermore, different changes in conformations were observed for each wild-type model compared to its N301A mutant counterpart and, interestingly, these N301A mutant model-specific glycan conformations were directly associated with the protein residues ultimately found to be exposed, which may explain the varied resistance to neutralising antibodies observed, in vitro, for the two N301A mutant strains.en_US
dc.identifier.urihttps://hdl.handle.net/10566/15270
dc.language.isoenen_US
dc.publisherUniversity of the Western Capeen_US
dc.rights.holderUniversity of the Western Capeen_US
dc.subjectHIV-1en_US
dc.subjectGlycansen_US
dc.subjectAntibodiesen_US
dc.subjectNeutralisation resistanceen_US
dc.subjectMolecular dynamicsen_US
dc.titleExploring the role of the “glycan-shield” of human immunodeficiency virus in susceptibility to, and escape from, broadly neutralising antibodiesen_US

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