Table 3.
Prioritized genes supported by multiple types of studies
| Gene symbol | Gene description | Prioritization method | Supporting source* | Functional annotation and/or literature support | ||||
|---|---|---|---|---|---|---|---|---|
| Seed-based | DE-based | Genet-Assoc | QTL | RNAi | Expr | |||
| IFI35 | interferon-induced protein 35 | + | + | + | + | 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) | + | + | + | + | 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 | + | + | + | The encoded protein is a member of the tripartite motif (TRIM) family. | |||
| IFIH1 | interferon induced with helicase C domain 1 | + | + | + | + | 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) | + | + | + | Involved in antigen processing and presentation. | |||
| FOLH1 | folate hydrolase (prostate-specific membrane antigen) 1 | + | + | + | ||||
| HLA-E | major histocompatibility complex, class I, E | + | + | + | 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 | + | + | + | 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 | + | + | + | |||||
| PLA2G7 | phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma) | + | + | + | 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) | + | + | + | + | 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) | + | + | + | + | + | 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 | + | + | + | + | 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 | + | + | + | 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 | + | + | + | 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 | + | + | + | 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) | + | + | + | + | + | 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 | + | + | + | 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 | + | + | + | + | + | + | |
*The following sources of supporting evidence were collected for each prioritized gene. Genet-Assoc: literature supporting for the gene’s genetic association with host resistance to influenza infection. QTL: candidate genes identified in the original QTL study with independent evidence (harboring founder variants that were associated with the phenotype; co-localization with a cis-eQTL; etc.). RNAi: host genes important for influenza life circle identified through high-throughput RNAi screens. Expr: host genes robustly up- or down- regulated after influenza virus infection identified from multiple microarray experiments. Detailed supporting evidence for each gene was listed in Additional file 2: Table S4. For more details of QTL, RNAi and expression studies, see Additional file 2: Table S5.