Table 3 Prioritized genes supported by multiple types of studies
From: Prioritizing genes responsible for host resistance to influenza using network approaches
Gene symbol | Gene description | Prioritization method | Supporting source* | Functional annotation and/or literature support | ||||
|---|---|---|---|---|---|---|---|---|
| Â | Â | Seed-based | DE-based | Genet-Assoc | QTL | RNAi | Expr | Â |
IFI35 | interferon-induced protein 35 | Â | + | Â | + | + | + | Ifi35 can be up-regulated upon exposure to interferon and modulate the cytokine signaling[35]. It also has antiviral properties against bovine foamy virus via inhibiting its replication[41]. |
EIF2AK2 | eukaryotic translation initiation factor 2-alpha kinase 2 | + | + | + | + | + | + | The encoded protein is a serine/threonine protein kinase that is activated after binding to dsRNA during the course of a viral infection. Mice lacking this gene displayed increased susceptibility to influenza virus infection[38]. |
TNF | tumor necrosis factor (TNF superfamily, member 2) | + | + | + | Â | Â | + | The encoded protein is a multifunctional proinflammatory cytokine, involved in the regulation of a wide spectrum of biological processes including apoptosis. It harbored polymorphisms associated with the severity of the clinical behavior after infection by the pandemic influenza A/H1N1[36]. |
TRIM26 | tripartite motif-containing 26 | + | Â | Â | + | + | Â | The encoded protein is a member of the tripartite motif (TRIM) family. |
IFIH1 | interferon induced with helicase C domain 1 | + | + | Â | + | Â | + | Innate immune receptor acting as a cytoplasmic sensor of viral nucleic acids and plays a major role in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. The Ifih1 knock-out mice exhibit an impaired response to different viral pathogens[51, 52]. |
TAP2 | transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) | Â | + | Â | + | Â | + | Involved in antigen processing and presentation. |
FOLH1 | folate hydrolase (prostate-specific membrane antigen) 1 | Â | + | Â | + | + | Â | Â |
HLA-E | major histocompatibility complex, class I, E | + | Â | Â | + | Â | + | HLA class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. |
LST1 | leukocyte specific transcript 1 | Â | + | Â | + | Â | + | The protein encoded by this gene is a membrane protein that can inhibit the proliferation of lymphocytes. In humans, LST1 plays a role in the regulation of the immune response to inflammatory diseases[53]. |
FAM135A | Â | Â | + | Â | + | + | Â | Â |
PLA2G7 | phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma) | Â | + | Â | + | Â | + | The encoded protein a secreted enzyme that catalyzes the degradation of platelet-activating factor to biologically inactive products. It harbored genetic polymorphisms associated with imflammatory diseases like atopy and asthma in humans[49]. |
TAPBP | TAP binding protein (tapasin) | + | + | Â | + | Â | + | Involved in the association of MHC class I with TAP and in the assembly of MHC class I with peptide. |
PSMB9 | proteasome (prosome, macropain) subunit, beta type, 9 (large multifunctional peptidase 2, LMP2) | + | + | + | Â | + | + | The proteasome is a multicatalytic proteinase complex. The encoded subunit is involved in antigen processing to generate class I binding peptides. The LMP2-mutant mice showed reduced levels of CD8+ T lymphocytes and generated 5- to 6-fold fewer influenza nucleoprotein-specific cytotoxic T lymphocyte precursors[37]. |
IL1RN | interleukin 1 receptor antagonist | + | Â | + | Â | + | + | The encoded protein inhibits the activities of interleukin 1 and modulates a variety of interleukin 1 related immune and inflammatory responses. It harbors genetic polymorphisms significantly related to humoral immune response to inactivated seasonal influenza vaccine[41]. |
C5 | complement component 5 | + | Â | + | + | Â | Â | The encoded protein is the fifth component of complement, which plays an important role in inflammatory and cell killing processes. The C5-deficiency was reported to increase susceptibility to mouse-adapted influenza A virus[39, 40]. |
DAXX | death-domain associated protein | Â | + | Â | Â | + | + | The encoded protein may function to regulate apoptosis. Influenza virus can escape the repressional function of Daxx during infection by binding matrix protein 1 with Daxx[54]. |
HLA-DQB1 | major histocompatibility complex, class II, DQ beta 1; similar to major histocompatibility complex, class II, DQ beta 1 | + | Â | + | + | Â | Â | HLA-DR7/4,DQB1*0302genotype was significantly associated (OR = 5.15; 95%CI = 1.94, 13.67; p = 0.001) with clinical hyporesponsiveness after trivalent inactivated influenza vaccine[35] |
MX1 | myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse) | + | + | + | + | Â | + | Mice susceptible to influenza infection harbor large exonic deletions or nonsense mutations in the Mx1 gene[22]. (seed gene) |
HLA-A | major histocompatibility complex, class I, A | + | Â | + | Â | + | Â | The magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and -B phenotype[27]. (seed gene) |
HLA-B | major histocompatibility complex, class I, B | + | + | + | + | + | + | |