Rotavirus Induces Epithelial–Mesenchymal Transition Markers by Transcriptional Suppression of miRNA-29b

Abstract

Acute gastroenteritis (AGE) is a serious global health problem and has been known to cause millions of infant deaths every year. Rotavirus (RV), a member of the Reoviridae family, still majorly accounts for the AGE in children below 5 years of age in India and worldwide. The involvement of miRNAs in the pathogenesis of RV has been suggested to be of the proviral as well as the anti-viral nature. miRNAs that promote the RV pathogenesis are capable of targeting the cellular components to evade the host anti-viral strategies. On the other hand, miRNAs with anti-rotaviral properties are themselves incapacitated during the progression of the infection. The exploitation of the epithelial–mesenchymal transition (EMT) as a pro-rotaviral strategy has already been identified. Thus, miRNAs that proficiently target the intermediates of the EMT pathway may serve as anti-viral counterparts in the RV–host interactions. The role of microRNA-29b (miR-29b) in the majority of human cancers has been well demonstrated, but its significance in viral infections is yet to be elaborated. In this study, we have assessed the role of miR-29b in RV-induced EMT and RV replication. Our study on miR-29b provides evidence for the recruitment of RV non-structural protein NSP1 to control the trans-repression of miR-29b in a p53-dependent manner. The trans-repression of miR-29b modulates the EMT pathway by targeting tripartite motif-containing protein 44 (TRIM44) and cyclin E1 (CCNE1). SLUG and SNAIL transcription repressors (downstream of TRIM44 and CCNE1) regulate the expression of E-cadherin, an important marker of the EMT. Also, it is established that ectopic expression of miR-29b not only constrains the EMT pathway but also restricts RV replication. Therefore, miR-29b repression is a crucial event in the RV pathogenesis. Ectopic expression of miR-29b displays potential anti-viral properties against RV propagation.

Protective effects of the postbiotic deriving from cow’s milk fermentation with L. paracasei CBA L74 against Rotavirus infection in human enterocytes

“…The RV infectivity is commonly demonstrated by the immunofluorescence staining of viral capsid protein VP6 in human enterocytes 17 , 18 . The RV infection of Caco-2 cells was confirmed by an increase of VP6 protein quantification and mRNA levels ( p < 0.001) (Fig.…”

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

“…Inhibition of cell cycle arrest is a common mechanism adopted by oncoviruses leading to cancer establishment in the host. Although RV has not been established as an oncovirus, our previous study has reported the involvement of RV in the manipulation of the cancer-associated epithelial-mesenchymal transition (EMT) pathway for efficient viral spread [ 9 ]. Apart from this, there have been other reports emphasizing the significance of cell cycle progression in RV pathogenesis [ 7 , 10 , 11 ].…”

“…The exploitation of the Wnt/ β-catenin pathway has been reported in other infections as well, be it bacterial infections such as Salmonella infection and tuberculosis, protozoan such Trypanosoma cruzi infection, or viral infections such as HIV [ 21 ]. As established in our previous studies, cell survival and proliferation are an imperative event for RV spread and pathogenesis, and involves a number of mechanisms to do so, such as manipulation of the Ca 2+ /Calmodulin pathway, the epithelial-mesenchymal transition pathway, and suppression of apoptosis [ 7 , 9 , 11 ]. This study supports the evidences of our previous findings that RV allows the host target cells to survive and propagate so that it may spread to other uninfected cells and build its pathogenesis in the host.…”

Herpesviridae and microRNAs

“…There have also been studies where mimics of miRNAs have proved to be useful in restricting viral replication. Recently, a study identifying the significance of miR-29b mimics have been reported to decrease the Rotavirus infection considerably [112] Likewise, mimics of miR-7704 and miR-101 could be encouraged in the HSV therapeutic research. Furthermore, the reported miRNA research could be compiled to develop therapeutic formulations involving combinations of mimics and inhibitors to synergistically suppress the HSV infection in the host.…”