miR-146a-5p promotes replication of infectious bronchitis virus by targeting IRAK2 and TNFRSF18

Abstract

Avian infectious bronchitis virus (IBV) is a coronavirus which infects chickens (Gallus gallus) of all ages and causes significant economic losses to the poultry industry worldwide. The present study aims to analyze the miRNAs related to pathogenicity of nephropathogenic IBVs. It was found that four miRNAs (miR-1454, miR-3538, miR-146a-5p and miR-215-5p) were related to the infection of virulent nephropathogenic IBV with transcript per million (TPM) > 500 and more than a 2-fold alteration. In vitro study results showed that the alterations of these four miRNAs were consistent with in vivo data. In vitro, we found that high levels of miR-146a-5p could enhance the replication of IBV at the early stage of infection, and its down regulated level could slow down the replication of IBV. Finally, high levels of exogenous miR-146a-5p in HD11 cells led to down regulation of IL-1 receptor associated kinase-2 (IRAK2) and Tumor necrosis factor receptor superfamily member 18 (TNFRSF18) genes. Luciferase reporter assays revealed that miR-146a-5p could bind to the 3'-UTRs of IRAK2 and TNFRSF18. This is the first study demonstrating that IBV induced miR-146a-5p is related to virus pathogenesis by down regulating IRAK2 and TNFRSF18, which may serve as a therapeutic strategy for the prevention of IBV infections.

Gga-miR-30d regulates infectious bronchitis virus infection by targeting USP47 in HD11 cells

“…In previous study, we used HD11 as an infection platform to study the changes in intracellular miRNAs after IBV infection, and found that miR-146a-5p could promote replication of IBV by targeting IRAK2 and TNFRSF18 [23]. In present study, we found another key miRNA gga-miR-30d regulating IBV replication by targeting USP47.…”

Identification and analysis of long non-coding RNAs and mRNAs in chicken macrophages infected with avian infectious bronchitis coronavirus

“…8 The competitive endogenous RNA (ceRNAs) network centered on gga-miR-30d and miR-146a-5p. The relationship between miRNAs and target genes has been shown [ 16 , 17 ]. The expression of the lncRNAs in the picture had changed significantly in IBV-infected HD11 cells, and they were predicted to interact with miRNAs at the nucleic acid sequence level …”

Screening druggable targets and predicting therapeutic drugs for COVID-19 via integrated bioinformatics analysis

“…For example, some researchers documented that miR-200c-3p could be upregulated via the NF-κB pathway to reduce ACE2 levels, this elevated angiotensin II levels and subsequently led to lung injury (Liu et al 2017 ). miR-146a-5p, one of the miRNAs targeting BSG, could enhance the replication of infectious bronchitis virus (one kind of coronavirus which infects chickens) at the early stage of infection by downregulating IL-1 receptor-associated kinase-2 (IRAK2) and TNF receptor superfamily member 18 (TNFRSF18) (Liu et al 2018 ). Through this miRNA–gene network, we could obtain more reliable information about the molecular mechanisms of COVID-19.…”