miR-21 promotes dengue virus serotype 2 replication in HepG2 cells

Area of Science:

• Virology
• Molecular Biology
• Public Health

Background:

• Dengue virus (DENV) infection is a major global health concern.
• MicroRNAs (miRNAs) are key regulators of gene expression.
• The role of specific miRNAs in DENV replication is not fully understood.

Purpose of the Study:

• To investigate the role of microRNAs (miRNAs) in Dengue virus 2 (DENV 2) replication.
• To identify specific miRNAs differentially expressed during DENV 2 infection.
• To evaluate miR-21 as a potential therapeutic target for DENV infection.

Main Methods:

• Screening of candidate miRNAs for expression changes in DENV 2-infected HepG2 cells.
• Treatment of cells with anti-miR-21 (AMO-21) and peptide nucleic acid-21 (PNA-21) constructs.
• Quantification of DENV 2 production and titer.
• Analysis of miR-21 regulation in Zika virus and DENV 4 infections.

Main Results:

• Seven miRNAs were found to be differentially expressed during DENV 2 infection, with miR-21 consistently altered.
• miR-21 expression was also dysregulated in antibody-dependent enhancement of DENV 2 infection and Zika virus infection.
• Inhibition of miR-21 using AMO-21 significantly reduced DENV 2 production.
• PNA-21 treatment alone increased DENV 2 titer, while the AMO-21/PNA-21 complex showed no significant difference from controls.

Conclusions:

• miR-21 plays a crucial role in promoting DENV 2 replication.
• Targeting miR-21 represents a promising therapeutic strategy for controlling dengue virus infections.
• The findings provide insights into the molecular mechanisms underlying DENV pathogenesis and potential interventions.