For example, the IFITM1
gene, which inhibits Zika virus, is expressed 73-fold less in Zika-infected cells than in neighboring uninfected cells.
Ectopic overexpression of Rec in pluripotent cells leads to significant upregulation of interferon-induced viral restriction factor IFITM1
and increased innate antiviral responses, suggesting that HERVK also induces viral restriction pathway in early embryos .
Both cell populations upregulated ISGs in response to viral infection, including factors that inhibit viral entry into the host cell (IFN-induced transmembrane protein 1 (IFITM1
)), intracellular replication of virus (eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and radical SAM domain-containing 2 (RSAD2), also known as viperin), and viral egress from the cell (IFN-stimulated gene 15 (ISG15)) (Figures 4(c) and 4(d), resp.).
Recently, IFITMs have become a popular research topic with the discovery that the immune-related IFITMs (IFITM1
, IFITM2, and IFITM3) inhibit the early replication of multiple viruses, including influenza A virus (IAV), dengue virus (DENV), West Nile virus (WNV), severe acute respiratory syndrome coronavirus (SARS CoV), hepatitis C virus (HCV), vesicular stomatitis virus (VSV), Ebola virus (EBOV), and human immunodeficiency virus type 1 (HIV-1) [3-8].
The IFN-stimulated gene IFITM3, a small membrane-associated IFN-inducible transmembrane protein 3, was shown to inhibit flaviviral replication.118 Recently, IFITM3 and IFITM1
were also shown to inhibit the replication of ZIKV.
IFN also induces transmembrane protein 1 (IFITM1
) which was reported to inhibit HCV entry .
Caption: FIGURE 1: The change of the coefficient of variation CV for 22 proteins: APOL6, CASP1, CNP, CXCL10, DHX58, DRAP1, DYNLT1, FAM46A, GEMIN4, GORASP1, IFITM1
, IRF7, PLSCR1, RTP4, SAMD9, SAMHD1, SIGLEC1, TAF1C, TLR7, TNFAIP6, TREX1, and ZBP1, The %-axis denotes the time (unit: h), It indicates that as the critical transition occurs, that is, the time evolves towards t = 45 h (see the vertical black line), the coefficient of variation CV for 22 proteins above significantly increases in the symptomatic group and has no obvious change in the asymptomatic group, Therefore, these 22 proteins can be viewed as DNBs for early-warning signals,
The predicted inhibition of the interferon-signaling pathway by KJ and APE was due to significant downregulation of six genes; IFI35, IFIT1, IFITM1
, IFITM3, IRFl, PSMB8 encoding interferon-induced protein 35, interferon-induced protein with tetratricopeptide repeats 1, interferon induced transmembrane protein 1, interferon induced transmembrane protein 3, interferon regulatory factor 1, and proteasome subunit beta type 8, respectively.
In addition, genes, including Krt15, Krt14, N-cadherin, cadherin-3, nestin, SOD2, Wnt4, Notch-1, SPON1, IFITM1
, ITM2A, CXCR4, DKK4, NGF, and its receptor TrkA, have been proposed as corneal limbal basal epithelial stem cell-specific markers [46-52].
In this study on glioma cells, the activation of numerous interferon-induced proteins (such as IFIT1, IFIT2, IFI27, IFITM1
, IFITM2, and G1P2) lends support to this mechanism of pathogenicity.
At p4, all five cell lines exhibited enhanced expression of nine genes (ZFP42, TDGF1, SFRP2, PODXL, NR6A1, CD9, DNMT3B, IFITM1
, and LIN28), which are all related to stemness, and reduced expression of four genes (TAT, PAX4, IAPP, and DDX4), which are related to differentiation (Figure 1(c)).