Host immune system gene targeting by a viral miRNA

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Virally encoded microRNAs (miRNAs) are found in herpesviruses, but their functions remain largely uncharacterized.
• MicroRNAs play critical roles in regulating gene expression and cellular processes.

Purpose of the Study:

• To investigate the biological roles of human cytomegalovirus (HCMV)-encoded miRNAs.
• To identify specific miRNA targets of HCMV and elucidate their impact on viral infection and host immunity.

Main Methods:

• Development of a novel algorithm for predicting miRNA targets.
• Application of the algorithm to HCMV miRNAs to identify potential gene targets.
• Experimental validation of predicted targets using molecular and cellular assays.

Main Results:

• The major histocompatibility complex class I-related chain B (MICB) gene was identified as a top target of hcmv-miR-UL112.
• HCMV infection leads to down-regulation of MICB expression by hcmv-miR-UL112.
• Down-regulation of MICB resulted in decreased natural killer (NK) cell receptor NKG2D binding and reduced NK cell-mediated killing of infected cells.

Conclusions:

• HCMV utilizes a miRNA-based mechanism for immune evasion.
• The hcmv-miR-UL112 down-regulation of MICB represents a novel viral strategy to impair NK cell surveillance and promote viral persistence.