N-terminal VP1 Truncations Favor T = 1 Norovirus-Like Particles.
Ronja PoganVictor U WeissKevin BondJasmin DülferChristoph KrispNicholas LykteyJürgen Müller-GuhlSamuele ZorattoGünter AllmaierMartin F JarroldCésar Muñoz-FontelaHartmut SchlüterCharlotte UetrechtPublished in: Vaccines (2020)
Noroviruses cause immense sporadic gastroenteritis outbreaks worldwide. Emerging genotypes, which are divided based on the sequence of the major capsid protein VP1, further enhance this public threat. Self-assembling properties of the human norovirus major capsid protein VP1 are crucial for using virus-like particles (VLPs) for vaccine development. However, there is no vaccine available yet. Here, VLPs from different variants produced in insect cells were characterized in detail using a set of biophysical and structural tools. We used native mass spectrometry, gas-phase electrophoretic mobility molecular analysis, and proteomics to get clear insights into particle size, structure, and composition, as well as stability. Generally, noroviruses have been known to form mainly T = 3 particles. Importantly, we identified a major truncation in the capsid proteins as a likely cause for the formation of T = 1 particles. For vaccine development, particle production needs to be a reproducible, reliable process. Understanding the underlying processes in capsid size variation will help to produce particles of a defined capsid size presenting antigens consistent with intact virions. Next to vaccine production itself, this would be immensely beneficial for bio-/nano-technological approaches using viral particles as carriers or triggers for immunological reactions.
Keyphrases
- mass spectrometry
- endothelial cells
- induced apoptosis
- sars cov
- mental health
- gene expression
- high resolution
- liquid chromatography
- late onset
- cell cycle arrest
- oxidative stress
- small molecule
- zika virus
- binding protein
- cell proliferation
- immune response
- drug induced
- aedes aegypti
- amyotrophic lateral sclerosis
- simultaneous determination