Rotavirus-Mediated Suppression of miRNA-192 Family and miRNA-181a Activates Wnt/β-Catenin Signaling Pathway: An In Vitro Study.

Anwesha Banerjee,Anupam Mukherjee,Mamta Chawla-Sarkar

doi:10.3390/v14030558

Anwesha Banerjee, Anupam Mukherjee + Show 1 more

Open Access

https://doi.org/10.3390/v14030558

Copy DOI

Abstract

The significance of the Wnt/β-catenin signaling cascade in Rotavirus (RV) infection has not been elucidated. In this study, we attempt to elucidate the importance of the Wnt/β-catenin pathway in the RV pathogenesis and investigate a miRNA-mediated approach to regulate the pathway to repress the RV infection in the host. The regulation of the Wnt signaling pathway in terms of β-catenin accumulation and activation was analyzed by Western blotting and Confocal imaging analysis. The expression levels of miR-192 family members and miR-181a were enquired into using qPCR assays, whereas their targets in the Wnt pathway were confirmed using the Luciferase Reporter Assays. Members of the miR-192 family and miR-181a, which target the components of the pathway, were also found to be considerably decreased in expression during RV infection. Ectopic expression of these miRNAs could restrict the RV pathogenesis by targeting the intermediates of the Wnt signaling pathway. The miR-192 family and miR-181a were capable of suppressing the RV infection via targeting of the Wnt/β-catenin pathway. The study not only highlights the role of the Wnt signaling cascade in RV infection but also suggests that miRNAs can synergistically decrease RV replication by a significant amount. Thus, the miR-192 family and miR-181a present themselves as prospective antivirals against RV infection.

Highlights

Before the introduction of the vaccines Rotarix® (RV1) and RotaTeq® (RV5), Rotavirus (RV) was considered to be the primary cause of fatal diarrhea in children below the age of five
After identifying the miRNAs that could interfere with the expressions of their targets in the Wnt pathway, we looked for changes in the expression levels of these respective miRNAs in RV infection
The initiation of the Wnt/β-catenin pathway is marked by the accumulation and activation of β-catenin in the cytoplasm followed by its translocation to the nucleus (Figure 1), where it acts as a transcriptional coactivator of cell survival and proliferation-associated genes of Cyclin D1 (CCND1), MYC, etc

Summary

Introduction

Before the introduction of the vaccines Rotarix® (RV1) and RotaTeq® (RV5), Rotavirus (RV) was considered to be the primary cause of fatal diarrhea in children below the age of five. The global RV detection rate had decreased from 42.5% in 2000 to about 37% by. India accounted for about 22% of the global death incidences due to RV, while being one of the four countries that account for about half of the total estimated deaths due to RV infection [1]. A four-year study (2016–2019) reported a decrease in Rotavirus-associated gastroenteritis (RVGE) cases with the acceptance of vaccines, most of the sufferers were infants below two years of age, with the most prevalent RV strains being different from those identified in previous studies [2].

Methods

Results

Discussion

Conclusion