INVESTIGATING HOW ANTI-PRM ANTIBODIES TURN IMMATURE DENGUE VIRUS INFECTIOUS

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.