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Volume 104, Issue 1

Knockdown of restricts dengue virus replication by augmenting interferon alpha-inducible protein 27 via the RIG-I pathway No Access

Abstract

The lncRNA plays a vital role in mitochondrial function and antiviral response. We have previously identified as dysregulated lncRNAs and found an inverse correlation with interferon alpha-inducible protein 27 (IFI27) expression associated with developing dengue severity. However, the role of in dengue virus (DV) infection remains elusive. Here, we undertook a study to evaluate the functional consequences of and IFI27 modulation on antiviral response and viral replication in dengue infection. We observed that the knockdown of augmented IFI27 expression and antiviral response via the RIG-I pathway. Increased antiviral response leads to a decrease in dengue viral replication. Further study suggested that the knockdown of IFI27 augmented expression of the activating transcription factor 3 (ATF3), a negative regulator of antiviral response, and increased dengue virus replication suggesting an important role played by IFI27 in mediating antiviral response. RNA sequencing study confirmed several mitochondrial genes significantly altered upon knockdown of in DV-infected cells. We further verified the effect of knockdown on mitochondrial functions. We observed a reduced level of phospho-DRP1(S616) expression along with elongated mitochondria in DV2-infected cells. Further, knockdown or ectopic expression of IFI27 increased mitochondrial ROS production and cell death via activation of caspase 3. Our study points to the crucial role of and IFI27 in mediating antiviral response and mitochondrial dysfunction in dengue infection.

  • Received:
  • Accepted:
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Keyword(s): antiviral response , ATF3 , dengue , IFI27 , ISG12a and NEAT1
Funding
This study was supported by the:
  • Department of Biotechnology, Ministry of Science and Technology, India (Award BT/PR8597/MED/29/764/2013)
    • Principle Award Recipient: ArupBanerjee
© 2023 The Authors
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/content/journal/jgv/10.1099/jgv.0.001823
2023-01-13
2024-04-20
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Knockdown of NEAT1 restricts dengue virus replication by augmenting interferon alpha-inducible protein 27 via the RIG-I pathway
J. Gen. Virol. 104, 001823 (2023); https://doi.org/10.1099/jgv.0.001823
/content/journal/jgv/10.1099/jgv.0.001823
/content/journal/jgv/10.1099/jgv.0.001823
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