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Abstract

Rabies, caused by rabies lyssavirus (RABV), is a fatal disease among humans and almost all warm-blooded animals. Our previous study showed that the long non-coding RNA (lncRNA) EZH2 degradation-associated lncRNA (EDAL) effectively inhibits RABV infection both and by degrading EZH2 and promoting the transcription of an antiviral gene, . Herein, we found that recombinant RABV expressing EDAL (rRABV-EDAL) restricts RABV replication in primary granule neurons but not in primary cortical neurons or astrocytes. Further study revealed that EDAL induced EZH2 protein degradation and thereby decreased trimethylation of lysine 27 on the histone 3 (H3K27me3) level in granule neuron cells but not in cortical neurons or astrocytes. Furthermore, rRABV-EDAL infection induces more mRNA transcription in granule neurons, while there are almost no obvious changes in cortical neurons or astrocytes. Consistently, compared with the parent virus RABV, reduced pathogenicity of rRABV-EDAL was observed in mice post-intranasal infection but not intramuscular infection. These results suggest that the lncRNA EDAL restricts RABV replication in a cell-specific and infection route-dependent manner.

Funding
This study was supported by the:
  • National Natural Science Foundation of China (Award 31872451)
    • Principle Award Recipient: LingZhao
  • China National Postdoctoral Program for Innovative Talents (Award BX2021109)
    • Principle Award Recipient: BaokunSui
  • China Postdoctoral Science Foundation (Award 2021M691170)
    • Principle Award Recipient: BaokunSui
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/content/journal/jgv/10.1099/jgv.0.001725
2022-03-02
2024-03-28
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