Exploring the interplay between miRNAs, apoptosis and viral load, in Dengue virus infection

Virology. 2024 Aug:596:110095. doi: 10.1016/j.virol.2024.110095. Epub 2024 May 1.

Abstract

Dengue virus (DENV) is a major global health concern, causing millions of infections annually. Understanding the cellular response to DENV infection is crucial for developing effective therapies. This study provides an in-depth analysis of the cellular response to Dengue virus (DENV) infection, with a specific focus on the interplay between microRNAs (miRNAs), apoptosis, and viral load across different DENV serotypes. Utilizing a variety of cell lines infected with four DENV serotypes, the research methodically quantifies viral load, and the expression levels of miRNA-15, miRNA-16, and BCL2 protein, alongside measuring apoptosis markers. Methodologically, the study employs quantitative PCR for viral load and miRNA expression analysis, and Western blot for apoptosis and BCL2 detection, with a statistical framework that includes ANOVA and correlation analysis to discern significant differences and relationships. The findings reveal that despite similar viral loads across DENV serotypes, DENV-2 exhibits a marginally higher load. A notable upregulation of miRNA-15 and miRNA-16 correlates positively with increased viral load, suggesting their potential role in modulating viral replication. Concurrently, a marked activation of caspases 3 and 7, along with changes in BCL2 protein levels, underscores the role of apoptosis in the cellular response to DENV infection. Conclusively, the study enhances the understanding of miRNA involvement in DENV pathogenesis, highlighting miRNA-15 and miRNA-16 as potential regulatory agents in viral replication and apoptosis. These findings pave the way for further exploration into miRNA-based therapeutic strategies against DENV infection.

Keywords: Apoptosis; BCL2 protein; Dengue virus; Therapeutic strategies; microRNAs.

MeSH terms

  • Apoptosis*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 7 / genetics
  • Caspase 7 / metabolism
  • Cell Line
  • Dengue Virus* / genetics
  • Dengue Virus* / physiology
  • Dengue* / virology
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Proto-Oncogene Proteins c-bcl-2* / genetics
  • Proto-Oncogene Proteins c-bcl-2* / metabolism
  • Serogroup
  • Viral Load*
  • Virus Replication*

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • MIRN16 microRNA, human
  • MIRN15 microRNA, human
  • BCL2 protein, human
  • Caspase 3
  • Caspase 7