Integrated miRNA and mRNA Expression Profiles Reveal Differentially Expressed miR-222a as an Antiviral Factor Against Duck Hepatitis A Virus Type 1 Infection.

Nana Sui,Zhijing Xie,Jingyu Wang,Shijin Jiang,Guige Xu,Jiaqing Hu,Honglei Yu,Yue Jiang,Yanli Zhu,Ruihua Zhang

doi:10.3389/fcimb.2021.811556

Abstract

Duck hepatitis A virus 1 (DHAV-1) is a highly contagious etiological agent that causes acute hepatitis in young ducklings. MicroRNAs (miRNAs) play important regulatory roles in response to pathogens. However, the interplay between DHAV-1 infection and miRNAs remains ambiguous. We characterized and compared miRNA and mRNA expression profiles in duck embryo fibroblasts cells (DEFs) infected with DHAV-1. In total, 36 and 96 differentially expressed (DE) miRNAs, and 4110 and 2595 DE mRNAs, were identified at 12 and 24 h after infection. In particular, 126 and 275 miRNA–mRNA pairs with a negative correlation were chosen to construct an interaction network. Subsequently, we identified the functional annotation of DE mRNAs and target genes of DE miRNAs enriched in diverse Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may be important for virus resistance, cell proliferation, and metabolism. Moreover, upregulated miR-222a could negatively regulate DHAV-1 replication in DEFs and downregulate integrin subunit beta 3 (ITGB3) expression by targeting the 3′ untranslated region (3′UTR), indicating that miR-222a may modulate DHAV-1 replication via interaction with ITGB3. In conclusion, the results reveal changes of mRNAs and miRNAs during DHAV-1 infection and suggest miR-222a as an antiviral factor against DHAV-1.

Highlights

Duck virus hepatitis (DVH) is a highly infectious and fast-spreading disease that has resulted in a high mortality rate among ducklings worldwide since its first isolation in 1949 (Levine and Fabricant, 1950; Liu et al, 2011; Shi et al, 2013; Zhang et al, 2020)
We reveal a negative correlation between miR-222a and integrin subunit beta 3 (ITGB3) and further demonstrate that miR-222a could suppress Duck hepatitis A virus 1 (DHAV-1) replication
cytopathic effect (CPE) and viral titers in duck embryo fibroblasts cells (DEFs) were measured at different time points after infection with LY0801 to evaluate the propagation kinetics of duck hepatitis A virus (DHAV)-1 infection

Summary

Introduction

Duck virus hepatitis (DVH) is a highly infectious and fast-spreading disease that has resulted in a high mortality rate among ducklings worldwide since its first isolation in 1949 (Levine and Fabricant, 1950; Liu et al, 2011; Shi et al, 2013; Zhang et al, 2020). The causative agent of DVH is duck hepatitis A virus (DHAV)—a nonenveloped, single-stranded, and positive-sense RNA virus of the Avihepatovirus genus of the Picornaviridae family (Delang et al, 2012; Mao et al, 2017). It’s one chain can direct the RNA-induced silencing complex to target mRNA sequences for subsequent translation suppression or target degradation (Holohan et al, 2012; Kelley et al, 2012). The interferon-induced miR-196 and miR-296 have perfect complementarity with the hepatitis C virus (HCV) genome and are involved in the antiviral process in Huh cells (Pedersen et al, 2007)

Methods

Results

Conclusion