genomewide characterization of host-pathogen interactions by ...

Maren Depke
Results
Host Cell Gene Expression Pattern in an in vitro Infection Model
CD274 alias programmed cell death 1 ligand 1 (PD-L1) is involved in the regulation of
inflammatory responses (Sharpe et al. 2007). In this study, CD274 gene expression was induced
2.5 h after start of infection and further increased at the 6.5 h time point. Interestingly, at the
later time point, the second PD-1 receptor, programmed cell death 1 ligand 2 (PDCD1LG2; 2.7),
was also induced.
The prostaglandin-endoperoxide synthase 2 (PTGS2) was less induced at the 6.5 h than at the
2.5 h time point (Table R.4.5). Additionally, the intensity values for PTGS2 at 6.5 h were lower in
both control and infected samples (60 and 94) when compared to the 2.5 h control sample (280).
This might hint for an early reaction that was about to stop at the later time point. Induction of
prostaglandin receptor PTGER4 still increased from 2.5 h to 6.5 h, and induction of another
receptor, PTGER2, was only detectable at the 6.5 h time point. The reaction of the genes for
these receptors seemed to lag behind the reaction of the gene coding for the enzyme responsible
for synthesis of their ligand.
Interferon-β (IFNB1) was induced at both analyzed time points. At the 2.5 h time point,
interferon reaction has already been described in reference to the induced genes IFIT2 and IFIT3
(page 117). In the IPA canonical pathway “Interferon Signaling” (page 119), IFI35, IFIT1, IFIT3,
IRF1, and others were included as induced, interferon-regulated genes at the 6.5 h time point,
and IFIH1 has already been introduced in the IPA canonical pathway “Role of Pattern Recognition
Receptors in Recognition of Bacteria and Viruses” (page 120). Manual filtering revealed further
six interferon regulated genes IFI16, IFI44L, IFIT2, IFIT5, IRF2, and ISG20 to be induced 6.5 h after
start of infection.
A histone cluster 1 gene (HIST1H2AB) was repressed significantly with a less than −1.5x fold
change 2.5 h after start of infection. But 6.5 h after infection, a number of 17 other histone
cluster 1 genes together with HIST1H2AB were repressed. Of these 17 additional genes, 4 had
already yielded a significant p-value at the 2.5 h time point, but did not pass the 1.5 fold cutoff.
Furthermore, H1 histone family member 0 (H1F0) and H2A histone family member X (H2AFX)
were repressed at the 6.5 h time point (Table R.4.5, Table R.4.6).
Cyclins CCNB1, CCNB2, and CCNH were repressed, while CCND1 and CCNL1 were induced
6.5 h after start of infection. In this context, induced cyclin-dependent kinases / kinase-like CDK6,
CDKL2, and CDKL5 were conspicuous at the 6.5 h time point, while cyclin-dependent kinase
inhibitors CDKN1B, CDKN2B, and CDKN3 were repressed. Contrarily, the inhibitor CDKN2C was
induced. Similarly, genes coding for cell division cycle associated proteins CDCA3, CDCA4, CDCA8,
and CDC25A, and genes encoding centromer/centrosomal proteins CENPF, CEP55, CEP97,
CEP120, and CEP250 were repressed, while CDC14A and CEP170 were induced. Regulatory genes
CKS2, GAS2L3, PRC1, and SKP2 were repressed, whereas BTG1, CHEK2, and DMTF1 were
observed as induced (Table R.4.6).
In a condensed manner, histones were repressed, some cyclin-dependent kinase (CDK) were
induced, and CDK inhibitors, cyclins, cell division cycle associated proteins, centromer/
centrosomal proteins and regulatory genes were found with both repressed and induced
examples. Nevertheless, repression held a bigger fraction of this subset of genes than induction.
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