概要 |
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 i...n 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 here show that a hyperfusogenic mutant MV (IC323-F(T461I)-EGFP), 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 the cell-to-cell viral transmission. The spread of IC323-F(T461I)-EGFP was inhibited by the fusion inhibitor peptide as well as by some but not all of 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.続きを見る
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