PRRSV alters m⁶A methylation and alternative splicing to regulate immune, extracellular matrix-associated function

Area of Science:

• Virology
• Molecular Biology
• Genomics

Background:

• Porcine reproductive and respiratory syndrome virus (PRRSV) infection significantly impacts swine health.
• The molecular mechanisms underlying PRRSV pathogenesis, particularly concerning host gene regulation, are not fully understood.

Purpose of the Study:

• To investigate the impact of PRRSV infection on host gene expression, alternative splicing, and N6-methyladenosine (m6A) modifications.
• To identify key genes and pathways involved in PRRSV pathogenesis.

Main Methods:

• Transcriptome sequencing (RNA-seq) and m6A individual-nucleotide-resolution crosslinking and immunoprecipitation sequencing (MeRIP-seq) were employed.
• Differential gene expression, alternative splicing events, and m6A modification sites were analyzed in PRRSV-infected and control pig lungs.

Main Results:

• 1624 differentially expressed genes (DEGs) were identified in PRRSV-infected pigs.
• Significant alterations in alternative splicing (54,367 events) and m6A modifications (2265 DASEs) were observed.
• Genes such as LMO7, ZNF185, and ECM1 showed altered expression and splicing, impacting downstream pathways involved in cell signaling and extracellular matrix regulation.

Conclusions:

• PRRSV infection profoundly affects host cell gene expression, alternative splicing, and m6A modification patterns.
• Altered expression of LMO7, ZNF185, and ECM1, and their downstream targets, may facilitate viral invasion and replication.
• These findings highlight potential therapeutic targets for PRRSV infections.