Structures of immature flavivirus particles

Area of Science:

• Virology
• Structural Biology
• Biophysics

Background:

• Dengue and yellow fever viruses are significant human pathogens.
• Understanding viral particle structure is crucial for developing antiviral strategies.
• The precursor membrane protein (prM) and envelope glycoprotein (E) play key roles in flavivirus assembly and infectivity.

Purpose of the Study:

• To determine the high-resolution structures of prM-containing dengue and yellow fever virus particles.
• To elucidate the organization of surface glycoproteins and their associated precursor proteins.
• To compare the structural features of these related flaviviruses.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to image virus particles.
• Image reconstruction techniques were applied to generate 3D structures.
• High-resolution structural analysis was performed on dengue and yellow fever virus particles.

Main Results:

• Structures were determined to 16 Å (dengue) and 25 Å (yellow fever) resolution.
• Both virus particles exhibit 60 icosahedrally organized trimeric spikes on their surface.
• Each spike comprises three prM:E heterodimers, with prM pre-peptides covering E glycoprotein fusion peptides, similar to alphaviruses.
• Transmembrane densities suggest coiled-coil interactions of E and prM proteins within the viral membrane.

Conclusions:

• Dengue and yellow fever viruses share highly similar structural organization of their surface proteins.
• The prM protein's pre-peptide acts as a protective cap for E glycoprotein fusion peptides, potentially regulating viral entry.
• The findings provide insights into flavivirus assembly, maturation, and potential therapeutic targets.