STRUCTURES OF ASYMME TRIC PARTICLES OF TBEV PROVIDE INSIGHT INTO FLAVIVIRUS ASSEMBLY AND MATURATION
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| Year of publication | 2025 |
| Type | Conference abstract |
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| Description | Immature particles of flaviviruses are coated by a membrane decorated by spikes, each formed by three heterodimers of pre pre-membrane (prM) and envelope (E) proteins 1 . Maturation requires cleavage of prM into pr and M fragments and rearrangement of the coat proteins into a smooth herringbone pattern of M M-E heterodimers 2 . Despite the global health impact of flaviviruses, their assembly and maturation are poorly understood 1,2 . Here, we show that most ticktick-borne encephalitis virus (TBEV) particles are asymmetric and lack subsets of surface heterodimers. Transmembrane and peripheral membrane helices of prM and E induce membrane bending, which is necessary for TBEV budding into the ER membrane. Immature particles of TBEV contain incomplete spikes, providing evidence that their coats assemble directly from prM prM-E heterodimers. Exposure of TBEV particles to acidic pH in the Golgi complex promotes maturation. The spikes and herringbone patterns in TBEV maturation intermediates are arbitrarily oriented relative to each other rather than being aligned to one icosahedral symmetry. Furthermore, the shapes of the bare membrane areas of TBEV virions and immature particles are different. Therefore, the mature herringbone pattern assembles from a randomly oriented nucleation center by gradually adding M M-E heterodimers to its edges as the spikes disassemble and prMs are cleaved. The incompleteness of the protein coats explains how flaviviruses can be neutralized by antibodies binding to parts of E proteins inaccessible at the surface of the spiky and herringbone structures, and opens possibilities for developing antivirals targeting the virus membrane. |
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