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Dynamic interplay between RNA N6-methyladenosine modification and porcine reproductive and respiratory syndrome virus

Zi-Han Wang1, Jing Li1, Sai-Ya Ma1

  • 1College of Life Sciences, School of Life Sciences and Green Development, Hebei University, Baoding, 071002, China.

Veterinary Research
|March 23, 2025
PubMed

Insights

N6-methyladenosine (m6A) RNA modifications regulate Porcine reproductive and respiratory syndrome virus (PRRSV) replication. Inhibiting m6A suppressed PRRSV, revealing potential therapeutic targets like MAPK14.

Area of Science:

  • Epigenetics
  • Virology
  • Molecular Biology

Background:

  • N6-methyladenosine (m6A) is a crucial epitranscriptomic modification influencing virus-host interactions.
  • Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to global swine health.
  • Understanding PRRSV's interaction with host cell epigenetic mechanisms is vital for disease control.

Purpose of the Study:

  • To investigate the role of m6A modification in PRRSV replication.
  • To identify m6A-enriched regions in the PRRSV genome.
  • To explore potential epigenetic targets for anti-PRRSV therapeutic strategies.

Main Methods:

  • m6A RNA immunoprecipitation sequencing (m6A-seq) to map m6A peaks on PRRSV genomic RNA.
  • Functional analysis to correlate m6A levels with PRRSV replication.
  • Treatment with the methylation inhibitor 3-deazaadenosine (3-DAA) to assess its effect on PRRSV replication.
  • Transcriptome-wide m6A profiling in PRRSV-infected cells.

Main Results:

  • Seven m6A-enriched peaks were identified in the PRRSV genomic RNA.
  • A positive correlation was observed between m6A modification levels and PRRSV replication.
  • 3-DAA treatment dose-dependently inhibited PRRSV replication.
  • Altered m6A modification was detected in 4677 transcripts during PRRSV infection, implicating MAPK14 and the p38/MAPK pathway.

Conclusions:

  • m6A RNA modification plays a significant role in regulating PRRSV replication.
  • Epigenetic targeting of m6A modification, particularly involving MAPK14, presents a promising therapeutic avenue against PRRSV.
  • These findings offer novel insights into the epigenetic landscape of PRRSV infection.
Keywords:
N 6-methyladenosine (m6a)m6A RNA immunoprecipitation sequencing (m6A-seq)p38/MAPK signalling pathwayporcine reproductive and respiratory syndrome virus (PRRSV)virus replication

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