Charge Detection Mass Spectrometry Reveals Norovirus GII.4 Virus-like Particles Failure to Complete
Lohra M Miller1, Benjamin E Draper2, Martin F Jarrold1
1Chemistry Department, Indiana University, 800 E Kirkwood Ave, Bloomington, Indiana 47405, United States.
Journal of the American Society for Mass Spectrometry
|July 15, 2025
Summary
Charge detection mass spectrometry revealed that norovirus GII.4 virus-like particles (VLPs) often form incomplete capsids. This finding is crucial for developing effective norovirus vaccines.
Area of Science:
- Virology
- Biophysics
- Structural Biology
Background:
- Norovirus is a major cause of gastroenteritis, and its virus-like particles (VLPs) are promising vaccine candidates.
- Norovirus VLPs can assemble into different capsid structures (T=1, T=3, T=4), with T=3 being the native structure.
Purpose of the Study:
- To accurately measure the masses of norovirus GII.4 VLPs using charge detection mass spectrometry (CD-MS).
- To determine the completeness of norovirus VLP capsids, which is challenging for other structural methods.
Main Methods:
- Utilized electrostatic linear ion trap-charge detection mass spectrometry (ELIT-CD-MS) for high-resolution mass measurements.
- Analyzed mass distributions of norovirus GII.4 VLPs to identify different capsid constructs (T=1, T=3, T=4).
Main Results:
- Observed peaks corresponding to T=1, T=3, and T=4 norovirus GII.4 VLP constructs.
- Mass measurements indicated that many capsids were incomplete, with missing subunits, rather than fully assembled icosahedra.
Conclusions:
- ELIT-CD-MS can accurately determine VLP mass and identify incomplete particles, information obscured by methods like cryo-electron microscopy.
- The prevalence of incomplete norovirus GII.4 VLPs has implications for VLP stability and vaccine efficacy.
