genomewide characterization of host-pathogen interactions by ...

Maren Depke
Results
Host Cell Gene Expression Pattern in an in vitro Infection Model
Table R.4.3: Differentially abundant proteins which exhibit differential gene expression.
gene name
description
UniProt
accession
number
EntrezGene
ID
protein
fold change a
transcript
2.5 h 6.5 h 2.5 h 6.5 h
ALCAM activated leukocyte cell adhesion molecule Q13740 214 4.5 4.3 1.1 1.8
APOL2 apolipoprotein L, 2 Q9BQE5 23780 2.1 4.5 1.2 4.5
ERAP1 endoplasmic reticulum aminopeptidase 1 Q9NZ08 51752 N/A 5.6 -1.0 1.6
IFIT2
interferon-induced protein with
tetratricopeptide repeats 2
P09913 3433 1.1 6.2 2.4 5.2
IFIT3
interferon-induced protein with
tetratricopeptide repeats 3
O14879 3437 1.1 2.6 1.6 3.4
OASL 2'-5'-oligoadenylate synthetase-like Q15646 8638 N/A 16.9 1.1 5.1
WARS tryptophanyl-tRNA synthetase P23381 7453 -1.3 1.6 1.1 4.4
FASN fatty acid synthase P49327 2194 -1.6 -1.6 -1.1 -1.7
KPNA2
karyopherin alpha 2 (RAG cohort 1, importin
alpha 1)
P52292 3838 -1.5 -1.7 -1.3 -1.7
PPME1 protein phosphatase methylesterase 1 Q9Y570 51400 -2.9 -18.0 -1.1 -1.9
CNP 2',3'-cyclic nucleotide 3' phosphodiesterase P09543 1267 -2.4 1.2 -1.1 1.6
IFIT1
interferon-induced protein with
tetratricopeptide repeats 1
P09914 3434 -2.1 1.3 1.6 3.3
ZC3HAV1 zinc finger CCCH-type, antiviral 1 Q7Z2W4 56829 -2.0 1.2 1.4 3.4
a Fold change values were calculated for the comparison of infected GFP + S9 cell with the baseline of medium control samples.
Differential regulation is indicated in bold.
Evaluation of infection-dependent differentially expressed genes using Ingenuity Pathway
Analysis (IPA) for the two time points 2.5 h and 6.5 h after start of infection
For each of the two analyzed time points, 2.5 h and 6.5 h after start of infection, a list with
genes differentially expressed in infected samples compared to controls was uploaded to
Ingenuity Pathway Analysis (IPA, www.ingenuity.com). Adequate fold change value accompanied
the EntrezGene identifiers. A minimal absolute fold change cutoff of 1.5 had been applied.
In the statistical testing performed by the different IPA tools, the size of the input list
influences the significance levels of the results. As the two lists were very different in size (40
genes at the 2.5 h time point vs. 1196 genes at the 6.5 h time point; Table R.4.1), the significance
levels for each analysis were by far not directly comparable. Therefore, the 2.5 h data were
examined separately and additionally served for illustration purposes like overlaying gene
expression data for 2.5 h on 6.5 h data results. The analysis concerning networks and pathways
was focused on the differential gene expression at the 6.5 h time point.
In the samples of the time point 2.5 h after infection, the big fraction of genes with increased
expression was noticeable (33 of 40 genes; Fig. R.4.5 B). Strongest induction (fold change 4.2)
was observed for IL-6, a cytokine occupying a key position in regulation of the immune response.
Another immune-stimulating cytokine, IFN-β, was strongly induced (IFNB1, fold change 2.8;
rank 4 of induced genes), and the response to interferon was seen in the induction of interferoninduced
proteins IFIT2 (fold change 2.4) and IFIT3 (fold change 1.6). IFN-β also influences IL-6
expression (Fig. R.4.6).
Interestingly, prostaglandin-endoperoxide synthase 2 transcription was induced (PTGS2 alias
Cox-2, fold change 2.3; rank 6 of induced genes). This enzyme generates the inflammation
mediators prostaglandin (PG) G 2 and H 2 from arachidonic acid. From PGH 2 , the other
prostaglandins like PGE 2 are formed by different synthases. In the data set, also PGE 2 receptor
PTGER4 was induced (and induction of PGE 2 receptor PTGER2 was seen only at the 6.5 h time
point). Therefore, prostaglandin synthesis as well as prostaglandin receptor were induced on
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