Zika: Defining the antigenic epitopes in the Zika virus envelope protein

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Zika virus belongs to the flavivirus genus and has 58% amino acid sequence identity to
dengue virus. Flaviviruses are enveloped viruses with a lipid membrane surrounded by an
outer protein shell consisting of two structural, transmembrane glycoproteins, prM and E. In
mature and infectious flaviviruses, the E protein forms a continuous icosahedral protein shell,
which contains encompasses the cellular attachment interfaces, and all of the dominant
neutralization antibody epiotpes. Moreover, the E protein catalyzes the fusion of the viral
membrane to the host cell membrane, the critical step in cell entry that delivers the viral
genome into the cytoplasm. We previously determined the crystal structures of the E proteins
from various flaviviruses, including dengue virus, in the pre- and postfusion conformations.
These structures provided detailed maps of the antigenic landscape of the virus, and revealed
the molecular mechanism of membrane fusion. Here, we propose to harness our expertise
and apply the experimental approaches we established in our previous work on flaviviruses to
determine the atomic structure of the Zika virus E protein, how it assembles in virus
particles, and how it catalyzes membrane fusion during cell entry. By identifying the structure
and composition of the complete antigenic surface of Zika virus, this work will provide a
powerful framework for the design and production of preventative and therapeutic treatments
including therapeutic antibodies, subunit-based vaccines and virus cell-entry inhibitors.