論文

査読有り
2018年3月1日

Cell-to-cell measles virus spread between human neurons is dependent on hemagglutinin and hyperfusogenic fusion protein

Journal of Virology
  • Yuma Sato
  • ,
  • Shumpei Watanabe
  • ,
  • Yoshinari Fukuda
  • ,
  • Takao Hashiguchi
  • ,
  • Yusuke Yanagi
  • ,
  • Shinji Ohno

92
6
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1128/JVI.02166-17
出版者・発行元
American Society for Microbiology

Measles virus (MV) usually causes acute infection but in rare cases persists in the brain, resulting in subacute sclerosing panencephalitis (SSPE). Since human neurons, an important target affected in the disease, do not express the known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), how MV infects neurons and spreads between them is unknown. Recent studies have shown that many virus strains isolated from SSPE patients possess substitutions in the extracellular domain of the fusion (F) protein which confer enhanced fusion activity. Hyperfusogenic viruses with such mutations, unlike the wild-type MV, can induce cell-cell fusion even in SLAM- and nectin 4-negative cells and spread efficiently in human primary neurons and the brains of animal models. We show here that a hyperfusogenic mutant MV, IC323-F(T461I)-EGFP (IC323 with a fusionenhancing T461I substitution in the F protein and expressing enhanced green fluorescent protein), but not the wild-type MV, spreads in differentiated NT2 cells, a widely used human neuron model. Confocal time-lapse imaging revealed the cell-to-cell spread of IC323-F(T461I)-EGFP between NT2 neurons without syncytium formation. The production of virus particles was strongly suppressed in NT2 neurons, also supporting cell-to-cell viral transmission. The spread of IC323- F(T461I)-EGFP was inhibited by a fusion inhibitor peptide as well as by some but not all of the anti-hemagglutinin antibodies which neutralize SLAM- or nectin-4- dependent MV infection, suggesting the presence of a distinct neuronal receptor. Our results indicate that MV spreads in a cell-to-cell manner between human neurons without causing syncytium formation and that the spread is dependent on the hyperfusogenic F protein, the hemagglutinin, and the putative neuronal receptor for MV.

リンク情報
DOI
https://doi.org/10.1128/JVI.02166-17
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29298883
ID情報
  • DOI : 10.1128/JVI.02166-17
  • ISSN : 1098-5514
  • ISSN : 0022-538X
  • PubMed ID : 29298883
  • SCOPUS ID : 85042465189

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