Octahedral small virus-like particles of dengue virus type 2

Area of Science:

• Structural biology
• Virology
• Immunology

Background:

• Flavivirus envelope (E) and precursor M (prM) proteins self-assemble into virus-like particles (VLPs).
• Maturation involves prM cleavage to M, converting immature VLPs to mature particles, mimicking authentic virions.
• Previous studies suggested icosahedral symmetry for smaller VLPs (smVLPs).

Purpose of the Study:

• To determine the cryo-electron microscopy (cryo-EM) structure of immature dengue virus type 2 smVLPs.
• To elucidate the symmetry and subunit organization of these particles.
• To relate the structural findings to the development of flavivirus vaccines.

Main Methods:

• Expression of flavivirus prM and E proteins.
• Isolation and purification of secreted VLPs.
• Cryo-electron microscopy (cryo-EM) for structural determination.

Main Results:

• Immature smVLPs exhibit octahedral symmetry, not the previously suggested icosahedral symmetry.
• The asymmetric unit is a trimer of prM-E heterodimers, forming a 72-heterodimer octahedral particle.
• Mature smVLPs are ovoid and possess virion-like fusion properties.

Conclusions:

• The octahedral symmetry of immature smVLPs provides a new understanding of flavivirus particle assembly.
• These structural insights are crucial for optimizing the use of VLPs as vaccine immunogens.
• The findings support the potential of non-infectious VLPs in developing specific flavivirus vaccines.