期刊
VETERINARY MICROBIOLOGY
卷 255, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.vetmic.2021.109025
关键词
Japanese encephalitis virus; Cellular secretory pathway; Lysosomes; RNA replication; Autophagy
资金
- National Natural Science Foundation of China [31830097, 31672586]
- Key Research and Development Program of Guangdong Province [2019B020218004]
- Earmarked Found for China Agriculture Research System [CARS-41-G16]
- Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2018)
- Young Scholars of Yangtze River Scholar Professor Program (2019)
The Japanese encephalitis virus manipulates cellular secretory pathways and autophagy components to create an optimal environment for genome replication. The virus replicates in lysosomes, not autophagosomes, and utilizes autophagic components for intracellular growth, shedding light on potential antiviral targets.
Japanese encephalitis virus is absolutely dependent on their host cells and has evolved various strategies to manipulate the cellular secretory pathways for viral replication. However, how cellular secretory pathways are hijacked, and the origin of the viral vesicles remains elusive during JEV replication. Here we show how JEV manipulates multiple components of the cellular secretory pathway, including autophagic machinery, to generate a superior environment for genome replication. We utilized double-strand RNA antibodies to label JEV RNA complex seeking the viral replication compartments and found that JEV genome replication takes place in lysosomes (LAMP1), not in autophagosomes (LC3). Subsequently, in situ hybridization results showed that viral RNAs (vRNAs) of JEV strongly colocalized with LAMP1. What surprised us was that JEV vRNAs markedly colocalized with LC3, indicating that autophagy plays an active role in JEV replication. Interestingly, we found that JEV utilized autophagic components for intracellular growth in an autophagy-dependent manner and the fusion of autophagosome-lysosome plays a positive role in JEV post-RNA replication processes. Collectively, our findings demonstrate that JEV can manipulate cellular secretory pathway to form genome replication organelles and exploit autophagy components for intracellular growth, providing new insights into the life cycle of JEV and uncovering an attractive target for antiviral drugs.
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