Structural studies of Chikungunya virus maturation

Area of Science:

• Virology
• Structural Biology
• Cryo-electron microscopy

Background:

• Alphavirus maturation involves cleavage of precursor glycoprotein p62 into E2 and E3.
• This cleavage is essential for generating fusion-competent spikes on mature virions.
• Understanding this process is key to controlling alphavirus infection.

Purpose of the Study:

• To elucidate the structural differences between immature and mature Chikungunya virus.
• To investigate the role of glycoprotein cleavage in alphavirus assembly and infectivity.
• To provide high-resolution structural insights into the immature viral state.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine the structure.
• A resolution of 6.8 Å was achieved for the immature Chikungunya virus.
• Site-directed mutagenesis was employed to inhibit glycoprotein cleavage.

Main Results:

• The immature virus exhibits less compact spikes with a larger radius compared to mature virions.
• Domains B on E2 glycoproteins in immature virus restrict movement, protecting fusion loops.
• The immature nucleocapsid is more compact, shielding a conserved ribosome-binding site.

Conclusions:

• Post-translational processing of spikes and nucleocapsid is critical for producing infectious alphaviruses.
• Structural differences in the immature state highlight the necessity of cleavage for viral maturation.
• These findings offer insights into the alphavirus life cycle and potential therapeutic targets.