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TitleStructures of asymmetric particles of tick-borne encephalitis virus provide insight into flavivirus assembly and maturation.
Journal, issue, pagesSci Adv, Vol. 12, Issue 27, Page eaee4765, Year 2026
Publish dateJul 3, 2026
AuthorsTibor Füzik / Maria Anastasina / Peter Pajtinka / Ausra Domanska / Lauri I A Pulkkinen / Lenka Šmerdová / Lucie Nepovímová / Petra Formanová-Pokorná / Petra Straková / Jiří Nováček / Daniel Růžek / Robert Vácha / Sarah J Butcher / Pavel Plevka /
PubMed AbstractFlaviviruses are globally distributed human pathogens. However, the mechanisms underlying flavivirus assembly and maturation remain poorly understood. Here, we show that many particles of tick-borne ...Flaviviruses are globally distributed human pathogens. However, the mechanisms underlying flavivirus assembly and maturation remain poorly understood. Here, we show that many particles of tick-borne encephalitis virus (TBEV) are asymmetric and lack subsets of surface heterodimers. Immature particles of TBEV contain incomplete spikes, providing evidence that their coats assemble directly from heterodimers of premembrane (prM) and envelope (E) proteins. Exposure of TBEV particles to acidic pH in the Golgi complex promotes maturation. The spikes and herringbone regions in TBEV maturation intermediates are oriented randomly rather than conforming to a common icosahedral symmetry. Consequently, the mature herringbone lattice forms around a randomly oriented nucleation center, expanding by addition of membrane-envelope heterodimers as the spikes disassemble and prMs are cleaved. The observed incompleteness of the protein coats explains, as an alternative to particle breathing, how flaviviruses can be neutralized by antibodies that bind to regions of E proteins normally inaccessible in the spiky or herringbone structures.
External linksSci Adv / PubMed:42397903 / PubMed Central
MethodsEM (single particle) / EM (subtomogram averaging)
Resolution3.57 - 10.96 Å
Structure data

55311

9swk

EMDB-55311, PDB-9swk:
Immature TBEV envelope spike with interaction partners underneath - SPA
Method: EM (single particle) / Resolution: 3.57 Å

EMDB-55312: Immature TBEV envelope spike with interaction partners underneath - STA
Method: EM (subtomogram averaging) / Resolution: 4.24 Å

EMDB-55313: Asymmetric reconstruction of immature TBEV particle with 2 missing pentamers
Method: EM (single particle) / Resolution: 9.41 Å

EMDB-55314: Asymmetric reconstruction of immature TBEV particle with 2 irregularities
Method: EM (single particle) / Resolution: 10.25 Å

EMDB-55315: Asymmetric reconstruction of immature TBEV particle with altered 5-fold
Method: EM (single particle) / Resolution: 10.96 Å

EMDB-55316: Asymmetric reconstruction of TBEV virion
Method: EM (single particle) / Resolution: 5.1 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • tick-borne encephalitis virus
KeywordsVIRUS / tick borne encephalitis virus / envelope / flavivirus / spike / asymmetric / immature particle / SPA

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