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N6-methyladenosine modification positively regulate Japanese encephalitis virus replication

Min Yao1, Zhirong Cheng1,2, Xueyun Li1,3

  • 1Department of Microbiology, Airforce Medical University, Xi'an, 710032, Shaanxi, China.

Virology Journal
|January 19, 2024
PubMed

Insights

N6-methyladenosine (m6A) modification positively regulates Japanese encephalitis virus (JEV) replication. METTL3 knockdown significantly reduces JEV replication and enhances the host immune response, revealing m6A

Area of Science:

  • Virology
  • Molecular Biology
  • Epigenetics

Background:

  • N6-methyladenosine (m6A) modification is found in viral RNA, regulating virus replication and host immunity.
  • The specific role of m6A in Japanese encephalitis virus (JEV) replication remained uninvestigated.

Purpose of the Study:

  • To investigate the role of m6A modification in regulating JEV replication in mouse neuroblast cells (neuro2a).

Main Methods:

  • Detection of m6A modification in the JEV genome during infection.
  • Analysis of METTL3 (an m6A writer) expression in infected mouse brain tissue.
  • siRNA-mediated knockdown of METTL3 to assess its impact on JEV replication and host innate immunity.

Main Results:

  • The JEV genome exhibits m6A modification in neuro2a cells.
  • JEV infection led to decreased METTL3 expression in mouse brain.
  • METTL3 knockdown significantly reduced JEV replication and progeny virus production at 48 hours post-infection (hpi).
  • METTL3 knockdown cells showed an increased innate immune response to JEV infection.

Conclusions:

  • m6A modification plays a positive role in JEV infection.
  • Distinct m6A signatures exist for both JEV and the host during infection.
  • This study enhances the understanding of m6A's role in Flaviviridae virus infections.
Keywords:
FlaviviridaJapanese encephalitis virusMETTL3MeRIP-seqN6-Methyladenosine modification

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