Marek's disease virus-encoded microRNA-M6-5p suppresses viral replication by targeting UL42

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• Marek's disease virus (MDV) causes significant economic losses in the poultry industry.
• MicroRNAs (miRNAs) are critical regulators of gene expression.
• MDV-encoded miR-M6-5p was previously shown to suppress viral replication, but the mechanism was unclear.

Purpose of the Study:

• To elucidate the molecular mechanism by which MDV miR-M6-5p suppresses viral replication.
• To identify the direct target of miR-M6-5p involved in viral replication.

Main Methods:

• Bioinformatic prediction of miRNA targets.
• Construction and analysis of a UL42-null MDV mutant.
• Assessment of viral DNA polymerase activity.
• Overexpression and knockout of miR-M6-5p.

Main Results:

• The viral UL42 transcript, encoding a DNA polymerase subunit, was identified as a direct target of miR-M6-5p.
• Deletion of UL42 abolished MDV replication by impairing DNA polymerase activity.
• miR-M6-5p negatively regulates viral DNA polymerase activity; its overexpression suppressed activity, while its knockout enhanced it.

Conclusions:

• miR-M6-5p restricts MDV replication by downregulating UL42, thereby impairing viral DNA polymerase activity.
• MDV utilizes its own miRNAs to modulate replication through the core DNA replication machinery.