Nonstructural protein ns1 of influenza virus disrupts mitochondrial dynamics and enhances mitophagy via ulk1 and bnip3

Jae Hwan Lee, Soo Jin Oh, Jeanho Yun, Ok Sarah Shin

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Nonstructural protein 1 (NS1) of influenza virus (IFV) is essential for evading interferon (IFN)-mediated antiviral responses, thereby contributing to the pathogenesis of influenza. Mitophagy is a type of autophagy that selectively removes damaged mitochondria. The role of NS1 in IFV-mediated mitophagy is currently unknown. Herein, we showed that overexpression of NS1 protein led to enhancement of mitophagy. Mitophagy induction via carbonyl cyanide 3-chlorophenylhydrazone treatment in IFV-infected A549 cells led to increased viral replication efficiency, whereas the knockdown of PTEN-induced kinase 1 (PINK1) led to the opposite effect on viral replication. Overexpression of NS1 protein led to changes in mitochondrial dynamics, including depolarization of mitochondrial membrane potential. In contrast, infection with NS1-deficient virus resulted in impaired mitochondrial fragmentation, subsequent mitolysosomal formation, and mitophagy induction, suggesting an important role of NS1 in mitophagy. Meanwhile, NS1 protein increased the phosphorylation of Unc-51-like autophagy activating kinase 1 (ULK1) and the mitochondrial expression of BCL2-interacting protein 3 (BNIP3), both of which were found to be important for IFV-mediated mitophagy. Overall, these data highlight the importance of IFV NS1, ULK1, and BNIP3 during mitophagy activation.

Original languageEnglish
Article number1845
JournalViruses
Volume13
Issue number9
DOIs
Publication statusPublished - 2021 Sept
Externally publishedYes

Bibliographical note

Funding Information:
Funding: This research was funded by the Basic Science Research Program of the National Research Foundation of Korea (NRF) by the Ministry of Science, ICT & Future Planning (NRF-2019R1A2C1005961), by Korea Health Technology R&D Project through the Korea Health Industry Development Insti- tute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI21C1252) and by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2016R1A5A2007009).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Antiviral immune responses
  • BNIP3
  • Influenza a virus
  • Mitophagy
  • NS1

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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