2023年1月27日
Collective fusion activity determines neurotropism of an en bloc transmitted enveloped virus.
Science advances
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- 巻
- 9
- 号
- 4
- 開始ページ
- eadf3731
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1126/sciadv.adf3731
Measles virus (MeV), which is usually non-neurotropic, sometimes persists in the brain and causes subacute sclerosing panencephalitis (SSPE) several years after acute infection, serving as a model for persistent viral infections. The persisting MeVs have hyperfusogenic mutant fusion (F) proteins that likely enable cell-cell fusion at synapses and "en bloc transmission" between neurons. We here show that during persistence, F protein fusogenicity is generally enhanced by cumulative mutations, yet mutations paradoxically reducing the fusogenicity may be selected alongside the wild-type (non-neurotropic) MeV genome. A mutant F protein having SSPE-derived substitutions exhibits lower fusogenicity than the hyperfusogenic F protein containing some of those substitutions, but by the wild-type F protein coexpression, the fusogenicity of the former F protein is enhanced, while that of the latter is nearly abolished. These findings advance the understanding of the long-term process of MeV neuropathogenicity and provide critical insight into the genotype-phenotype relationships of en bloc transmitted viruses.
- リンク情報
- ID情報
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- DOI : 10.1126/sciadv.adf3731
- PubMed ID : 36706187
- PubMed Central 記事ID : PMC9882980