Two host microRNAs influence WSSV replication via STAT gene regulation

Area of Science:

• Molecular Biology
• Virology
• Aquaculture Immunology

Background:

• MicroRNAs (miRNAs) are key regulators of gene expression, often manipulated by viruses to enhance replication.
• The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is critical for host antiviral defense mechanisms.
• White spot syndrome virus (WSSV) is a significant pathogen affecting shrimp aquaculture.

Purpose of the Study:

• To investigate the role of specific shrimp microRNAs in modulating the host's antiviral response to WSSV.
• To elucidate the mechanism by which these microRNAs influence the JAK/STAT signaling pathway and viral replication.
• To identify potential targets for therapeutic intervention against WSSV infection in shrimp.

Main Methods:

• Identification and characterization of differentially expressed miRNAs in shrimp during WSSV infection.
• Quantitative analysis of miRNA, STAT, and dynamin (Dnm) gene expression.
• RNA interference (RNAi) for miRNA and gene knockdown.
• In vivo experiments involving recombinant protein injection.

Main Results:

• Two shrimp miRNAs, miR-9041 and miR-9850, were found to up-regulate WSSV replication.
• These miRNAs suppress STAT expression, leading to down-regulation of downstream Dnm genes (Dnm1, Dnm2, Dnm3).
• Knockdown of these miRNAs or silencing of STAT/Dnm genes restricted WSSV replication, while recombinant Dnm proteins inhibited it in vivo.

Conclusions:

• Host miR-9041 and miR-9850 enhance WSSV replication by targeting the JAK/STAT pathway in Macrobrachium rosenbergii.
• STAT and its downstream Dnm genes play a crucial role in the antiviral defense against WSSV.
• These findings highlight a novel mechanism of viral evasion and offer potential targets for WSSV control strategies.