N-terminal VP1 truncations favor T=1 norovirus-like particles

Pogan, R.; Weiss, V. U.; Bond, K.; Duelfer, J.; Krisp, C.; Lyktey, N.; Mueller-Guhl, J.; Zorrato, S.; Allmaier, G.; Jarrold, M. F.; Munoz-Fontela, C.; Schlueter, H.; Uetrecht, C.

doi:10.1101/2020.11.25.396499

bioRxiv · 10.1101/2020.11.25.396499

N-terminal VP1 truncations favor T=1 norovirus-like particles

Pogan, R.·Weiss, V. U.·Bond, K.·Duelfer, J.·Krisp, C.·Lyktey, N.·Mueller-Guhl, J.·Zorrato, S.·Allmaier, G.·Jarrold, M. F.·Munoz-Fontela, C.·Schlueter, H.·Uetrecht, C.

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Abstract

Noroviruses cause immense sporadic gastroenteritis outbreaks worldwide. Emerging genotypes, which are divided based on VP1 sequence, 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 are characterized in detail using a set of biophysical and structural tools. We are using native mass spectrometry, gas-phase electrophoretic mobility molecular analysis and proteomics to get clear insights into particle size, structure, composition as well as stability. Generally, noroviruses have been known to form mainly T=3 particles. Importantly, we identify a major truncation in the capsid proteins as a likely cause for the formation of merely 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.

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Pogan, R., Weiss, V. U., Bond, K., Duelfer, J., Krisp, C., Lyktey, N., Mueller-Guhl, J., Zorrato, S., Allmaier, G., Jarrold, M. F., Munoz-Fontela, C., Schlueter, H., Uetrecht, C.. 2020-11-26. N-terminal VP1 truncations favor T=1 norovirus-like particles. https://doi.org/10.1101/2020.11.25.396499

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