Abstract

BackgroundDuck hepatitis A virus type 3 (DHAV-3) is one of the most harmful pathogens in the duck industry. However, the molecular mechanism underlying DHAV-3 infection in ducklings remains poorly understood. To study the genetic regulatory network for miRNA-mRNA and the signaling pathways involved in DHAV-3 infection in ducklings, we conducted global miRNA and mRNA expression profiling of duckling liver tissues infected with lethal DHAV-3 by high-throughput sequencing.ResultsWe found 156 differentially expressed miRNAs (DEMs) and 7717 differentially expressed genes (DEGs) in livers of mock-infected and DHAV-3-infected duckling. A total of 19,606 miRNA-mRNA pairs with negatively correlated expression patterns were identified in miRNA-mRNA networks constructed on the basis of these DEMs and DEGs. Moreover, immune-related pathways, including the cytokine-cytokine receptor interaction, apoptosis, Toll-like receptor, Jak-STAT, and RIG-I-like receptor signaling pathway, were significantly enriched through analyzing functions of mRNAs in the network in response to DHAV-3 infection. Furthermore, apl-miR-32-5p, apl-miR-125-5p, apl-miR-128-3p, apl-miR-460-5p, and novel-m0012-3p were identified as potential regulators in the immune-related signaling pathways during DHAV-3 infection. And some host miRNAs were predicted to target the DHAV-3 genome.ConclusionsThis is the first integrated analysis of miRNA and mRNA in DHAV-3-infected ducklings. The results indicated the important roles of miRNAs in regulating immune response genes and revealed the immune related miRNA-mRNA regulation network in the DHAV-3-infected duckling liver. These findings increase our knowledge of the roles of miRNAs and their target genes in DHAV-3 replication and pathogenesis. They also aid in the understanding of host-virus interactions.

Highlights

  • Duck hepatitis A virus type 3 (DHAV-3) is one of the most harmful pathogens in the duck industry

  • The results indicated that differentially expressed miRNAs (DEMs) might play an important role in the virus-host interactions during the duck hepatitis A virus (DHAV)-3 infection in duck

  • Global transcriptome profiles In parallel with the miRNA profile, we explored the global changes in gene expression associated with DHAV-3 infection to assess the effect of DEMs on their predicted targets

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Summary

Introduction

Duck hepatitis A virus type 3 (DHAV-3) is one of the most harmful pathogens in the duck industry. Duck viral hepatitis is a highly fatal, contagious, and rapidly spreading viral infection in young ducklings [1]. The most widely distributed causative agent is duck hepatitis A virus (DHAV), which is classified as genus Avihepatovirus in the family Picornaviridae [2]. Based on phylogenetic analysis and virus neutralization tests, DHAV has been classified into DHAV-1, the most widespread serotype [3], DHAV-3, a serotype isolated in Korea and China [4, 5], and DHAV-2, a serotype isolated only in Taiwan [6]. With the widespread use of the officially approved DHAV-1 live vaccine in 2013, a higher rate of DHAV-3 causing DHAV infections has been observed in China [7].

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