Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/135780
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dc.titleINVESTIGATING HOW ANTI-PRM ANTIBODIES TURN IMMATURE DENGUE VIRUS INFECTIOUS
dc.contributor.authorMELISSA WIRAWAN
dc.date.accessioned2017-05-26T18:00:14Z
dc.date.available2017-05-26T18:00:14Z
dc.date.issued2017-02-06
dc.identifier.citationMELISSA WIRAWAN (2017-02-06). INVESTIGATING HOW ANTI-PRM ANTIBODIES TURN IMMATURE DENGUE VIRUS INFECTIOUS. ScholarBank@NUS Repository.
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/135780
dc.description.abstractDengue virus (DENV) is initially assembled as an immature particle with heterotrimeric spikes of envelope (E) and pre-membrane (prM) proteins. The large proportion of anti-prM antibodies in DENV-infected patients suggests presence of immature DENV particles. Fully immature DENV is non-infectious on its own but can turn infectious towards Fcγ-receptor-bearing cells when complexed with anti-prM antibody. After endocytosis, maturation involving dissociation of pr-peptides is crucial for infectivity. It is however, unknown how pr-peptides dissociate at low pH as the dissociation requires exposure to neutral pH. Here, using cryo-Electron Microscopy, we determined the structures of immature DENV-anti-prM Fab complex at pH 8.0 and 5.0, simulating environment before cell entry and after endocytosis. At pH 5.0, there were fewer Fabs on the virus and the E protein had been rearranged. Furthermore, presence of Fab enhanced virus particles-liposomes interaction. Taken together, our results suggest anti-prM antibodies assist in entry and interaction with endosomal membrane.
dc.language.isoen
dc.subjectmaturation, dengue, infectivity, antibody, enhancement, cryoEM
dc.typeThesis
dc.contributor.departmentDEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL)
dc.description.degreePh.D
dc.description.degreeconferredDOCTOR OF PHILOSOPHY
dc.identifier.isiutNOT_IN_WOS
Appears in Collections:Ph.D Theses (Open)

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