1887

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Volume 103, Issue 5

HBV induced the discharge of intrinsic antiviral miRNAs in HBV-replicating hepatocytes via extracellular vesicles to facilitate its replication No Access

Abstract

Hepatitis B virus (HBV), which can cause chronic hepatitis B, has sophisticated machinery to establish persistent infection. Here, we report a novel mechanism whereby HBV changed miRNA packaging into extracellular vesicles (EVs) to facilitate replication. Disruption of the miRNA machinery in hepatocytes enhanced HBV replication, indicating an intrinsic miRNA-mediated antiviral state. Interference with EV release only decreased HBV replication if there was normal miRNA biogenesis, suggesting a possible link between HBV replication and EV-associated miRNAs. Microarray and qPCR analyses revealed that HBV replication changed miRNA expression in EVs. EV incubation, transfection of miRNA mimics and inhibitors, and functional pathway and network analyses showed that EV miRNAs are associated with antiviral function, suggesting that to promote survival HBV coopts EVs to excrete anti-HBV intracellular miRNAs. These data suggest a novel mechanism by which HBV maintains its replication, which has therapeutic implications.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): extracellular vesicles , hepatitis B virus , intracellular environment , miRNA , viral persistence and viral replication
Funding
This study was supported by the:
  • National Science and Technology Major Projects of China (Award 2017ZX10202202, 2018ZX10301208)
    • Principle Award Recipient: ChenJieliang
  • the Chinese Academy of Medical Sciences (Award 2018PT31044, 2019-I2M-5–040)
    • Principle Award Recipient: ChenJieliang
  • Shanghai Municipal Education Commission (Award 201701070007E00057)
    • Principle Award Recipient: JieliangChen
  • Shanghai Science and Technology Committee (Award 18JC1411102)
    • Principle Award Recipient: JieliangChen
  • Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (Award No. 2017BT01S131)
    • Principle Award Recipient: ZhenghongYuan
  • Research Unit of Chronic Hepatitis B virus infection from China Academy of Medical Science (Award No. 2019RU037)
    • Principle Award Recipient: ZhenghongYuan
  • National Natural Science Foundation of China (Award No. 91842309)
    • Principle Award Recipient: ZhenghongYuan
  • National Natural Science Foundation of China (Award 81974304 and 82022043)
    • Principle Award Recipient: ChenJieliang
© 2022 The Authors
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2022-05-23
2024-04-20
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HBV induced the discharge of intrinsic antiviral miRNAs in HBV-replicating hepatocytes via extracellular vesicles to facilitate its replication
J. Gen. Virol. 103, 001744 (2022); https://doi.org/10.1099/jgv.0.001744
/content/journal/jgv/10.1099/jgv.0.001744
/content/journal/jgv/10.1099/jgv.0.001744
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