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-Structure paper
タイトル | Chikungunya virus assembly and budding visualized in situ using cryogenic electron tomography. |
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ジャーナル・号・ページ | Nat Microbiol, Vol. 7, Issue 8, Page 1270-1279, Year 2022 |
掲載日 | 2022年6月30日 |
著者 | David Chmielewski / Michael F Schmid / Graham Simmons / Jing Jin / Wah Chiu / |
PubMed 要旨 | Chikungunya virus (CHIKV) is a representative alphavirus causing debilitating arthritogenic disease in humans. Alphavirus particles assemble into two icosahedral layers: the glycoprotein spike shell ...Chikungunya virus (CHIKV) is a representative alphavirus causing debilitating arthritogenic disease in humans. Alphavirus particles assemble into two icosahedral layers: the glycoprotein spike shell embedded in a lipid envelope and the inner nucleocapsid (NC) core. In contrast to matrix-driven assembly of some enveloped viruses, the assembly/budding process of two-layered icosahedral particles remains poorly understood. Here we used cryogenic electron tomography (cryo-ET) to capture snapshots of the CHIKV assembly in infected human cells. Subvolume classification of the snapshots revealed 12 intermediates representing different stages of assembly at the plasma membrane. Further subtomogram average structures ranging from subnanometre to nanometre resolutions show that immature non-icosahedral NCs function as rough scaffolds to trigger icosahedral assembly of the spike lattice, which in turn progressively transforms the underlying NCs into icosahedral cores during budding. Further, analysis of CHIKV-infected cells treated with budding-inhibiting antibodies revealed wider spaces between spikes than in icosahedral spike lattice, suggesting that spacing spikes apart to prevent their lateral interactions prevents the plasma membrane from bending around the NC, thus blocking virus budding. These findings provide the molecular mechanisms for alphavirus assembly and antibody-mediated budding inhibition that provide valuable insights for the development of broad therapeutics targeting the assembly of icosahedral enveloped viruses. |
リンク | Nat Microbiol / PubMed:35773421 / PubMed Central |
手法 | EM (サブトモグラム平均) |
解像度 | 23.0 Å |
構造データ | EMDB-26448: Half-bud CHIKV assembly/budding intermediate from virus-infected human cells |