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|Title:||INVESTIGATING HOW ANTI-PRM ANTIBODIES TURN IMMATURE DENGUE VIRUS INFECTIOUS||Authors:||MELISSA WIRAWAN||Keywords:||maturation, dengue, infectivity, antibody, enhancement, cryoEM||Issue Date:||6-Feb-2017||Citation:||MELISSA WIRAWAN (2017-02-06). INVESTIGATING HOW ANTI-PRM ANTIBODIES TURN IMMATURE DENGUE VIRUS INFECTIOUS. ScholarBank@NUS Repository.||Abstract:||Dengue 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.||URI:||http://scholarbank.nus.edu.sg/handle/10635/135780|
|Appears in Collections:||Ph.D Theses (Open)|
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