Cryo EM structures of immature dengue virus - anti prM antibody complex at neutral and low pH show how antibody turns virus infectious — ASN Events
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  2. Session Ten - Poster Session C including Refreshments
  3. Cryo EM structures of immature dengue virus - anti prM antibody complex at neutral and low pH show how antibody turns virus infectious

Cryo EM structures of immature dengue virus - anti prM antibody complex at neutral and low pH show how antibody turns virus infectious (#371)

Melissa Wirawan 1 2 , Qian Zhang 1 2 , Scott Smith 3 4 , Thiam-Seng Ng 1 2 , Victor Kostyuchenko 1 2 , Guntur Fibriansah 1 2 , James Crowe 4 5 , Shee-Mei Lok 1 2
  1. Duke NUS graduate medical school, Singapore
  2. Centre for BioImaging Sciences, National University of Singapore, Singapore
  3. Department of Medicine, Vanderbilt University, Nashville, TN, USA
  4. The Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, USA
  5. Departments of Pediatrics and Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA

Immature dengue virus (immDENV) is often detected in a typical mature DENV preparation. ImmDENV is non-infectious as the uncleaved pr-peptide on the virus caps the fusion loop on the envelope protein, preventing virus-endosomal membrane fusion. Surprisingly, when complexed with antibody, immDENV can infect Fc-gamma bearing cells, showing its importance in pathogenesis. Here, we report the cryo-electron microscopy structures of immDENV complexed with an anti-pre-membrane (prM) human monoclonal antibody at neutral or low pH, mimicking the environment before cell entry or in the endosome, respectively. When pH was lowered, less antibodies were detected on the virus surface and the envelope proteins had undergone rearrangement. These results suggest how antibodies can aid pr-peptide dissociation from virus surface, and show the intermediate structures of the maturation process.