Project A03

Principal Investigator

Prof. Dr. Thomas Peters & Dr. Patrick Behrendt

Universität zu Lübeck & Medizinische Hochschule Hannover

A3

PhD candidate

Nachiket Moti

A3

Project Summary

Probing interactions of Hepatitis E virus (HEV) capsid proteins with attachment factors and neutralizing antibodies using NMR

The lifecycle of Hepatitis E virus (HEV), particularly attachment and entry, is poorly understood. HEV is an emerging zoonotic virus, chiefly responsible for acute hepatitis. Despite studies in the past attempting to characterise cellular factors responsible for the entry of this virus, the results remain largely inconclusive. It is crucial to study the interaction of the viral capsid protein with cellular factors and neutralising antibodies to better describe the mechanism of attachment and entry. This project aims to identify attachment factors and binders for the viral capsid protein using NMR spectroscopy as a main tool. The same approach will allow us to map the binding of neutralizing antibodies and in combination with complementary structure biology techniques available in VISION we may be able to uncover some of the cornerstones of attachment to host cells.

A3

References

  1. Huang Y, Reddy KD, Bracken C, et al. Environmentally Ultrasensitive Fluorine Probe to Resolve Protein Conformational Ensembles by 19F NMR and Cryo-EM. J Am Chem Soc. 2023;145(15):8583-8592. doi: 10.1021/jacs.3c01003.
  2. Mallagaray A, Creutznacher R, Dülfer J, et al. A post-translational modification of human Norovirus capsid protein attenuates glycan binding. Nat Commun. 2019;10(1):1320. doi: 10.1038/s41467-019-09251-5.
  3. Maass T, Westermann LT, Creutznacher R, et al. Assignment of Ala, Ile, LeuproS, Met, and ValproSmethyl groups of the protruding domain of murine norovirus capsid protein VP1 using methyl-methyl NOEs, site directed mutagenesis, and pseudocontact shifts. Biomol NMR Assign. 2022;16(1):97-107. doi: 10.1007/s12104-022-10066-7.
  4. Creutznacher R, Maass T, Dülfer J, et al. Distinct dissociation rates of murine and human norovirus P-domain dimers suggest a role of dimer stability in virus-host interactions. Commun Biol. 2022 Jun 9;5(1):563. doi: 10.1038/s42003-022-03497-4. 
  5. Creutznacher R, Maass T, Ogrissek P, et al NMR Experiments Shed New Light on Glycan Recognition by Human and Murine Norovirus Capsid Proteins. Viruses. 2021 Mar 5;13(3):416. doi: 10.3390/v13030416.