Capsid protein structure in Zika virus reveals the flavivirus assembly process

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Flavivirus particle structures, including Dengue and Zika viruses, are resolved at near-atomic levels, detailing surface protein arrangements (E, prM, M).
• The internal capsid proteins:RNA complex structure remains poorly understood due to inherent protein dynamics.

Purpose of the Study:

• To elucidate the quaternary organization and interactions of capsid proteins within immature Zika virus particles.
• To investigate the role of capsid proteins in the flavivirus assembly process.

Main Methods:

• Stabilization of immature Zika virus using a specific antibody targeting E and prM proteins.
• Determination of the virus particle structure at subnanometer resolution using cryo-electron microscopy.
• Computational fitting of capsid protein models into the electron density map.

Main Results:

• A subnanometer resolution structure of the capsid protein:RNA core was obtained.
• The structure revealed a previously uncharacterized helical feature of the capsid protein, presumed lost during proteolysis.
• Detailed arrangement of capsid proteins, their orientation relative to the lipid membrane and RNA, and interactions with surface protein transmembrane regions were illuminated.

Conclusions:

• The capsid protein plays a central role in the flavivirus assembly process.
• The stabilized structure provides novel insights into the internal organization of flaviviruses.
• The findings challenge previous assumptions about capsid protein structure and processing.