Table 3 Functions of the 10 most differentially expressed genes in ILTV vaccine infection

C1QTNF3 (CTRP3)

• C1q and tumor necrosis factor related protein 3, a. k. a. CTRP3.

• Functions are described in the Result and Discussion.

AQP5

• Aquaporin 5, a water channel protein.

• Functions are described in the Result and Discussion.

CCK

• Cholecystokinin

• Functions are described in the Result and Discussion.

SPINK5

• Serine peptidase inhibitor, Kazal type 5 or chicken ovomucoid

• Lymph-epithelial Kazal-type-related inhibitor (LEKTI).

• Suppresses cellular functions related to inflammation in human primary keratinocytes (HK) [34].

• Down-regulation of SPINK5 at all dpi may support the reduced cell death caused by vaccine ILTV infection.

THBS2

• Thrombospondin 2, a potent inhibitor of tumor growth and angiogenesis and a matricellular glycoprotein which mediates cell-to-cell interaction [35].

• Functions in angiogenesis in patients with early-stage non-small cell lung cancer [36], and wound healing and development of exuberant granulation tissue in horses [37].

• Up-regulation of THBS2 in vaccine ILTV infection may function in virus spread in infected cells.

PPIF

• Peptidylprolyl isomerase F, one of the peptidyl-prolyl cis-trans isomerase (PPIase) family proteins and a member of the mitochondrial permeability transition (PT) pore in the inner mitochondrial membrane.

• Stimulates the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins [38, 39].

• Apoptosis and necrosis of cells were induced by the activation of the PT pore [40–42].

• Down-regulation of PPIF genes in vaccine ILTV infection may play a role in cell death and recovery of cells.

VLDVR

• Very low density lipoprotein/vitellogenin receptor

• Binds to baculovirus surface membrane to inhibit ligand-receptor interaction in viral infection of HeLa cells [43].

• The meaning of down-regulation of VLDLR in ILTV vaccine infection in addition to in other herpesvirus infection, is unknown.

NMU

• Neuromedin U, a multifunctional neuropeptide

• Functions in conditions of pain and stress, the metabolism and homeostasis of feeding and energy in body, inflammatory diseases, smooth muscle contraction, and the control of blood flow and pressure [44, 45].

• Induces early-phase inflammation through the degranulation in mast cells in which NMU-R1 is highly expressed [46].

• Acts as an inflammatory mediator via the acceleration of IL-6 production in macrophages [47].

• Down-regulation of NMU may represent the inhibition of cellular factors associated with inflammation.

ADAM28

• A disintegrin and metalloproteinase (ADAM) domain 28.

• Functions in cell-to-cell and cell-to-matrix interaction on the cell surface for cancer cell proliferation, invasion and metastasis [48, 49].

• Up-regulated at carcinoma cells and functions the proliferation and progression of human lung and breast cancer cells [50, 51].

• Acts as an inhibitor against human dental pulp stem cells (HDPSCs) proliferation and an inducer of apoptosis of HDPSCs through the stimulation of alkaline phosphatase (ALP) secretion and dentin sialophosphoprotein (DSPP) [52].

• Degrades Insulin-like growth factor (IGF) binding protein 3 (IGFBP3) [53].

• The decreased expression of ADAM28 in vaccine ILTV infection, may suppress the active induction of apoptosis.

FST

• Follistatin

• Inhibits follicle-stimulating hormone [54].

• Binds and neutralizes activin, a paracrine hormone of TGF-β superfamily, which is related to the regulation of cell proliferation, apoptosis, and carcinogenesis [55, 56].

• A member of fibrotic and wound healing response genes and cellular proliferation genes and plays a role in muscle growth and strength in nonhuman primates and liver proliferation. Moreover, the small plaque mutant of VZV down-regulates FST [57].

• Up-regulation of FST at early phase (1 dpi) of vaccine ILTV infection may play a role in the initiation of cytopathic effect.