1887

Abstract

Flaviviruses assemble at the endoplasmic reticulum in an immature, non-infectious state that is designed to inhibit premature fusion with the host. Maturation of the particle occurs when it enters the trans-Golgi network, where low pH induces a conformational rearrangement of the virus glycoproteins. This transition causes 60 prM-E glycoprotein trimers in the immature virus to rearrange into 90 M-E dimers in the mature virus. We hypothesize that flaviviruses do not have exact icosahedral symmetry, thus providing flexibility for the large conformational rearrangements that are required during the virus life cycle. When icosahedral symmetry constraints were excluded in calculating the cryo-EM reconstruction of immature Kunjin virus (KUNV), a low virulent strain of West Nile virus, the nucleocapsid core touched the inside of the viral lipid membrane at the “proximal pole” and was asymmetrically positioned within the lipid bilayer envelope. The outer glycoprotein spikes on the “distal pole” were either distorted or missing. In the asymmetric reconstruction of mature KUNV, the core was re-positioned, as expected, concentric with the glycoprotein shell and there remained a distortion of the glycoproteins on one pole of the virion. This suggests that the interactions between the core and glycoproteins are altered during viral assembly and budding from the ER. In addition, it implies that the glycoproteins have a geometric defect that perhaps facilitates the transitions that occur during maturation. This defect in number and arrangement of the glycoproteins may reflect the consequence of membrane budding.

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/content/journal/acmi/10.1099/acmi.imav2019.po0005
2019-12-01
2020-01-24
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http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.imav2019.po0005
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