Table 3.
Immune genes differentially expressed between the RR and SS groups that were predicted as targets of the HVL-DE miRNAs at 20 dpc.
| Target genea | Immune functionb | HVL-DE miRNAs, SS, vs. RRc |
|---|---|---|
| Toll-like leucine-rich repeat protein (TL/LRR) | Activator, inflammatory responses to pathogens, Innate immunity | ↑ miR-731-5p |
| Signal transducer and activator of transcription 3 (STAT3) | Activator, acute-phase response, host-virus interaction, regulation of type I interferon signaling pathway, viral process | ↓ let-7d-c-1-3p ↑ ssa-miR-18b-3p |
| Signal transducer and activator of transcription 2 (STAT2) | Activator, antiviral defense, host-virus interaction, cytokine-mediated signaling pathway, regulation of type I interferon signaling pathway, viral process | ↓ let-7d-c-1-3p, ↑ miR-18b-3p |
| Tumor necrosis factor alpha-1 (TNF-alpha-1) | Activator, inflammatory response, I-kappaB kinase/NF-kappaB signaling, extrinsic apoptotic signaling pathway via death domain receptors, humoral immune response | ↑ miR-novel-5-3p |
| E3 ubiquitin-protein ligase TRIM39-like (LOC106608979) | Activator, positive regulation of apoptotic signaling pathway | ↑ miR-7a-2-6-3p |
| Interferon regulatory factor 3 (IRF3) | Activator, transcription factor activating innate immunity pathway, antiviral defense against DNA and RNA viruses, host-virus interaction | ↓ miR-8159-5p ↑ miR-18b-3p ↑ miR-21b-3p ↓ ↑ miR-29a-3p ↑ miR-29b-3-5p ↑ miR-29de-3p ↑ miR-29c-3p ↑ miR-novel-5-3p |
| Interferon regulatory factor 7 (IRF7) | Activator, transcription factor activator that promote inflammation, antiviral defense against DNA and RNA viruses, critical for the late than for the early phase of the IFN gene induction. | ↓ miR-192a-5p ↓ miR-459-3p ↑ miR-731-5p |
| C-C motif chemokine 19 (CCL19) | Cytokine, virus responsive gene, immune response, Inflammatory response, innate immunity pathway | ↑ miR-26a-3-3p ↑ miR-731-3p |
| Thioredoxin-interacting protein (TXNIP) | Transcriptional repressor, required for the maturation of natural killer cells, positive regulation of apoptotic process | ↓ let-7a-1-3-3p ↓ miR-8159-3p |
| Angiopoietin-related protein 4 precursor (ANGL4) | Inhibitor, negative regulation of apoptotic process | ↓ miR-192a-1-3p ↓ miR-192b-5p ↑ miR-29a-5p ↑ miR-29e-5p ↑ miR-7a-2-6-3p |
| C-X-C motif chemokine 10 precursor (CXL10) | Pro-inflammatory cytokine, involved in chemokine-mediated signaling pathway, immune response | ↑ miR-21b-3p ↓ |
| C-X-C chemokine receptor type 3 (CXCR3) | Receptor for C-X-R chemokines, regulates biological processes such as immune response, inflammatory, response, and apoptotic process | ↓ miR-8159-5p ↑ miR-731-5p (2x) ↑ miR-7a-2-6-3p |
| Interleukin-4 receptor alpha chain precursor (IL4RA) | Receptor, cytokine-mediated signaling pathway, immune response, production of molecular mediators involved in inflammatory response | ↑ miR-novel-5-3p |
| Interleukin-10 receptor beta chain precursor (I10R2) | Receptor, virus responsive gene, cytokine-mediated signaling pathway, antiviral defense response, immune response, inflammatory response | ↑ miR-18b-3p ↑ miR-221-5p ↑ miR-29b-2-5p ↑ miR-29c-5p (2x) |
| Probable ATP-dependent RNA helicase DHX58 (DHX58) | Virus responsive gene, host-virus interactions, innate immune response to RNA viruses and some DNA viruses such as poxviruses, negative regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling | ↑ miR-731-5p |
| Interferon-induced protein with tetratricopeptide repeats 5-like (IFIT5) | Virus responsive gene, defense response to virus, innate immune response, negative regulation of viral genome replication, positive regulation of I-kappaB kinase/NF-kappaB signaling | miR-2184-3p ↓ |
| XIAP-associated factor 1 (XAF1) | Virus responsive gene, pro-apoptotic gene, regulation of apoptotic process | ↓ miR-122-5p ↑ miR-146d-1-3p ↑ miR-29b-3-5p |
| Macrosialin precursor (CD68) | Virus responsive gene | ↓ let-7b-3p ↑ miR-731-5p ↑ miR-462a-3p (5x) |
| Interferon-induced transmembrane protein 5 (IFM5) | Virus responsive gene | ↑ miR-21b-3p ↓ |
| Receptor-transporting protein 3 (RTP3) | Virus responsive gene | ↑ miR-29a-3p, ↑ miR-29de-3p, ↑ miR-29c-3p |
| IFN-inducible protein Gig2-like-1 | Virus responsive gene | ↑ miR-462a-3p |
| Interferon-induced protein 44 (IFI44) | Virus responsive gene, antiviral defense, immune response | ↑ miR-21b-3p ↓ |
| Barrier-to-autointegration factor (BAF) | Virus responsive gene, host-virus interaction, known be exploited by retroviruses to facilitate integration of retroviruses in host genomes | ↑ miR-21b-3p ↓ |
| VHSV-induced protein-like (LOC100194553) | Virus responsive gene, immune response | ↑ miR-221-5p, ↑ miR-29b-1-5p ↓ ↑ miR-29c-5p miR-29d-5p ↓ |
| VHSV-inducible protein (VHSV) | Virus responsive gene, upregulated in VHSV | ↓ let-7d-c-1-3p, miR-29d-5p ↓ |
a
Target genes names as annotated in the Uniprot database (43).
b
The description of immune functions are based on GO terms in the Uniprot database and Krasnov et al. (45).
c
HVL-DE miRNAs with target site matches in the 3'UTRs of the target genes. For space saving reasons the ‘ssa'prefix was removed. Upward arrows (↑) illustrate higher expression, and downward arrows (↓) indicate lower expression in the SS group vs. the RR group at 20 dpc. In cases where the HVL-DE miRNAs showed large changes in different directions, the arrow prior to miRNA name denotes change in SS, and arrow behind miRNA denotes change in RR (Figure 5). If a miRNA has multiple matches to a target this is indicated in the following brackets.