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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
   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 + + + + + +
  1. *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 file2: Table S4. For more details of QTL, RNAi and expression studies, see Additional file2: Table S5.