[Seminar] IMpaCT- Double Seminar on Tick-Borne Encephalitis Virus

Title: Molecular Organisation of Tick-Borne Encephalitis Virus 

Speaker: Aušra Domanska, University of Helsinki, Finland

Abstract: Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species, with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilising membrane protein arrangement in the virion. The residues responsible for M protein interactions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions.

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Title: Structure of the immature tick-borne encephalitis virus 

Speaker: Maria Anastasina, University of Helsinki, Finland

Abstract: Tick–borne encephalitis virus (TBEV) in the Flavivirus genus is an important human pathogen that is currently on the rise in Europe. The shell of the TBEV consists of membrane (M) and envelope (E) heterodimers lying on the surface of the membrane. E is responsible for receptor interaction and membrane fusion during entry. On the TBEV assembly pathway, fusion incompetent, immature particles are produced as intermediates. They differ from mature virions, having trimeric spikes formed of three prM-E dimers, where prM is a precursor of M. During maturation, structural rearrangement of prM and E, prM cleavage by furin, and pr peptide dissociation are all required to produce the virion.

Using electron cryo-microscopy and image processing, we determined the structure of immature tick-borne encephalitis virus. We generated a model of the icosahedrally-symmetric immature TBEV, and using localised reconstruction we built a higher resolution model of the trimeric prM3E3 spike. The structure reveals fusion regulation by prM, which obscures the E fusion loop within the heterodimer, preventing untimely fusion. The membrane helices of M, instead of packing against E are clustered under the trimer, presumably preventing spike collapse and E dimerisation. By comparing the immature and mature atomic models, we are forming an accurate view of crucial events in TBEV maturation.

Webinar link, here.