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Comparison of differential expressed between EBOV and MARV infection in human and bat cells JUN is up-regulated (9X) after 23 h p.i. in human cells (SFig. 9). Likewise CYR61 is re-up-regulated after a phase of low expression after 7 h in human cells (SFig. 9). JUN is activated by MAPK8 and other kinases (JUN N-terminal kinases). MAPK8 (also known as JNK) has been reported to initiated the expression of CYR61 and was found as differential expressed im human cells 3 h p.i. in both infection states (SFig. 7). Specifically, CYR61 induces after coxsackievirus B3 infektion via JNK and to cause cell death [1]. HSV-1 infection of tumors was reported to also up-regulate CYR61 [2]. MAP3K12 is among the differentially expressed genes in human cells. However, a subtle fold change of approx. 1.5-fold is only seen in EBOV infected human cells after 23 h p.i.. FAM46C has been reported to be associated to yellow fever virus infection. This is an interferon type-1 stim- ulated gene (ISG) that enhances viral replication [3]. In the EBOV and MARV expression data a down-regulation of FAM46C is seen across all time points in human and bat cells. The list provided by [3] produces inconsistent results in the analysed data set. MCOLN2, an activator of viral replication is down- in EBOV and up-regualted in MARV infected human cells. A homologous gene in the bat transcriptome was not detected. A slight down-regulation with no changes in the time course is seen for ADAR in both infection models. The PLAU, plasimongen activator, urokinase gene is slightly up-regulated over the timecourse. This gene is involved in the dissolution of the fibrin clot. This observation is supported by the expression of the interaction partner SERPINA5 (SFig. 7). While slightly up-regulated after 3 h p.i. the gene shows a strong fold change decrease at 23 h time and shows an overall lower expression in human cells (read max: 33) compared to the bat cell line (read max: 479). Also VTN, another potential binding partner, is affected by differential transcription in human cells (SFig. 7). Here, also the anticoagulant ANXA3 together with its co-expressed gene (VIM) are up in both, EBOV and MARV infected human cells, at 23 h (see SFig. 9). A similar expression profile could be observed for ANKRD1. This gene shows not only a differential expression in human cells, but also in bat cells 7 h p.i.. The Reactome (curated pathway database, v51) pathway analysis in general reports the stronges, though non- significant ”enrichment” in fatty acid related pathways, specifically in chylomicron associated genes. A not siginficantly enriched Reactome pathway is reported for APOA1, CYP1A1 and ANKRD1. APOA1 has been studied in the context of HCV infections. Amphiphatic alpha helices are deemed to be crucial for viral particle formation. ANKRD1 is massively up-regulated after 23 h in human cells while there are no significant changes at earlier time points of this investigation. A similiar repeat (ANKRD23) shows up after 7 h to be comparably strong up- regulated in both EBOV and MARV infected human cells (SFig. 8). IL8 responds in both MARV and EBOV infected human cells with a massive significant up-regulation. The signif- icance was also observed by other used methods, however, the early transcriptome contains no expression at all and the later extracted transcriptome includes only a few reads. Interestingly, CREBBP, a TF that has a wide range of attributed functions and associations, is massively up-regulated in EBOV at 23 h, while there is a slight down-regulation in MARV in human cells. A similar pattern could be observed for EBOV infected bat cells. The transcription factor TFAP4 that also activates viral genes is down-regulated over the time course in human cells. Among the TFs that are present in viral promotors such as CREB3 and ATF3, ATF3 shows a strong up-regulation in EBOV and a slight, though not significant, up-regulation in MARV in human cells (SFig. 8). In both infection models, this up-regulation is only seen after 23 h, while there is virtually no response at the first two timepoints in human cells. An similar pattern could be observed for the bat cell line (up-regulation after 23 h p.i. in EBOV and MARV), although the fold change is much lower compared to human cells. The ZC3HAV1 (a zinc finger CCCH-type) induces an innate immunity to viral infections by preventing the accumu- lation of viral RNAs in the cytoplasm. It seems to recruit the RNA processing exosome to degrade the target RNAs and was shown to inhibit alphavirus and filovirus replication. It is down-regulated in EBOV while MARV shows no or even up-regulation in human cells. In bat cells no significant change could be observed. 2

Supplementary Figure 1: Scatterplot showing the log2 expression fold changes of coding and non-coding RNAs in human cells 3 h after EBOV and MARV infection, respectively. Outliers are labeld.

Supplementary Figure 2: Scatterplot showing the log2 expression fold changes of coding and non-coding RNAs in human cells 7 h after EBOV and MARV infection, respectively. Outliers are labeld. 3

Supplementary Figure 3: Scatterplot showing the log2 expression fold changes of coding and non-coding RNAs in human cells 23 h after EBOV and MARV infection, respectively. Outliers are labeld.

Supplementary Figure 4: Scatterplot showing the log2 expression fold changes of coding and non-coding RNAs in bat cells 3 h after EBOV and MARV infection, respectively. Outliers are labeld. 4

Supplementary Figure 5: Scatterplot showing the log2 expression fold changes of coding and non-coding RNAs in bat cells 7 h after EBOV and MARV infection, respectively. Outliers are labeld.

Supplementary Figure 6: Scatterplot showing the log2 expression fold changes of coding and non-coding RNAs in bat cells 23 h after EBOV and MARV infection, respectively. Outliers are labeld. 5

Supplementary Figure 7: Timeseries human 3h p.i. with EBOV or MARV. Human genes that have a similar or approximately time-course with respect to their differential expression are grouped. The angle defined by the differential expression 3 h p.i. was used for the grouping.

Supplementary Figure 8: Timeseries human 7h p.i. with EBOV or MARV. Human genes that have a similar or approximately time-course with respect to their differential expression are grouped. The angle defined by the differential expression 7 h p.i. was used for the grouping. 6

Supplementary Figure 9: Timeseries human 23h p.i. with EBOV or MARV. Human genes that have a similar or approximately time-course with respect to their differential expression are grouped. The angle defined by the differential expression 23 h p.i. was used for the grouping.

Supplementary Figure 10: Timeseries bat 3h p.i. with EBOV or MARV. Bat genes that have a similar or approximately time-course with respect to their differential expression are grouped. The angle defined by the differential expression 3 h p.i. was used for the grouping. 7

Supplementary Figure 11: Timeseries bat 7h p.i. with EBOV or MARV. Bat genes that have a similar or approximately time-course with respect to their differential expression are grouped. The angle defined by the differential expression 7 h p.i. was used for the grouping.

Supplementary Figure 12: Timeseries bat 23h p.i. with EBOV or MARV. Bat genes that have a similar or approximately time-course with respect to their differential expression are grouped. The angle defined by the differential expression 23 h p.i. was used for the grouping. 8

Supplementary Table 1: : Common features of filovirus infection. To com- pare the differential expression of Mock/EBOV and Mock/MARV in human and bat cells, log2 fold changes as computed by DEseq were visualized using scatter plots. Outliers (highly up-/down-regulated genes during both, EBOV and MARV infection in human and bat cells) were collected and further investigated based on the different scatter plots (see electronical Supplement) and listed here with their function. If publications concerning the immune response and/or viruses could be found for a gene, the corresponding Pubmed identifiers (PMID) were additionally listed. bold – interesting outliers with known relation to the immune response and/or viruses.

Gene Function PMID Human up-regulated 3 h p.i. FDXR Ferredoxin reductase; mitochondrial flavoprotein; initiates electron transport for cy- tochromes P450 receiving electrons from NADPH BEX4 Nerve Growth Factor Receptor-Associated Protein NDRG2 belongs to the alpha/beta hydrolase superfamily; may play a role in neurite outgrowth; 24383128 may be involved in glioblastoma carcinogenesis CYR61 matricellular protein; CYR61 is highly expressed at sites of inflammation and 15890942 wound repair, and is associated with diseases involving chronic inflammation and 22129992 tissue injury; wound healing and fibrosis CDK3 cyclin-dependent kinase; involved in cell cycle control; promotes entry into S phase 21067790 and promote exit from G0 IL32 Interleukin 32; cytokine that may play a role in innate and adaptive immune 24553842 responses; related to many viruses 24579465 20889550 TUBA1A ; found in morphologically differentiated neurologic cells HSD17B10 Hydroxysteroid (17-Beta) Dehydrogenase 10; functions in mitochondrial tRNA mat- 18984158 uration; it may contribute to the neuronal dysfunction associated with Alzheimer dis- 9338779 ease APBB3 member of the APBB protein family; binds to the intracellular domain of the 23064081 Alzheimer’s disease beta-amyloid precursor protein (APP) as well as to other APP- like ; related to inflammation and neurological disease DCTN1 encodes the largest subunit of ; involved in a diverse array of cellular func- tions, including ER-to-Golgi transport, the centripetal movement of and endosomes, spindle formation, movement, nuclear positioning, and ax- onogenesis OS9 Osteosarcoma Amplified 9; lectin which functions in ER quality control and ER- 25010283 associated degradation (ERAD) GTPBP2 GTP binding protein 2; GTPBP1 was shown to be upregulated by Interferon Gamma DTX3 functions as an E3 ubiquitin ligase; tight-binding, strong inhibitor of several G1 cy- 11226752 clin/Cdk complexes and a negative regulator of cell proliferation; related to Notch signaling and neurogenesis LOC100189589 DCTN1-AS1; DCTN1 antisense RNA 1; ncRNA Human down-regulated 3 h p.i. SYCP3 synaptonemal complex protein 3; this gene encodes an essential structural component of the synaptonemal complex; this complex is involved in synapsis, recombination and segregation of meiotic CDKN1C Cyclin-Dependent Kinase Inhibitor; tight-binding, strong inhibitor of several G1 cy- clin/Cdk complexes and a negative regulator of cell proliferation CDKN2AIPNL CDKN2A Interacting Protein N-Terminal Like MAP3K10 MAP kinase Continued on next page 9

Supplementary Table 1 – continued from previous page Gene Function PMID PCDHB4 neural cadherin-like cell adhesion proteins; interact in a homophilic manner to specify differential cell-cell connections mi3198-2 (=NR 039851.1?); identification of new microRNAs in paired normal and tumor tissue suggests a dual role for the ERBB2/HER2 gene TSPAN16 tetraspanin 16; transmembrane protein; no function specified PCDHB4 potential calcium-dependent cell-adhesion protein; may be involved in the establish- ment and maintenance of specific neuronal connections in the brain TMEM81 transmembrane protein 81 ZNF717 zinc finger protein 717 23912677 MAK male Germ Cell-Associated Kinase; essential for the regulation of ciliary length and required for the long-term survival of photoreceptors RAB3D member of RAS oncogene family; critical for secretory granule maturation (here neu- ropeptides and hormones are stored) LOC100506966 reported as an uncaracterized ncRNA, WITHDRAWN Human up-regulated 7 h p.i. PZP pregnancy-zone protein; is able to inhibit all four classes of proteinases by a unique ’trapping’ mechanism; associated with Alzheimer’s and Senile Plaques ANKRD23 Ankyrin repeat domain-containing protein 23; protein-protein interactions; found in a number of speeches and even viruses (horizontal transfer?) SNRPE Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleo- proteins; plays an important role in the splicing of cellular pre-mRNAs SIVA1 Apoptosis regulatory protein Siva; important role in the apoptotic (programmed cell death) pathway induced by the CD27 antigen LOC100506668 =NRAV (long non-coding RNA); negative regulator of antiviral response 25525793 (non-protein coding); modulates antiviral responses through suppression of interferon-stimulated gene transcription LOC100287559 =ADPGK-AS1; ADPGK antisense RNA 1 (long ncRNA), really new, no publications LOC100287375 reported as an uncaracterized ncRNA, WITHDRAWN TMEM17 Transmembrane Protein 17 RIN2 small GTPase involved in membrane trafficking in the early endocytic pathway MAML2 Mastermind-like protein 2 Human down-regulated 7 h p.i. RANBP3L RAN binding protein 3-like ELF5 E74-like factor 5 (ets domain transcription factor) CXCL12 stromal cell-derived factor 1 (SDF-1) also known as C-X-C motif chemokine 12 (CXCL12) is a chemokine protein; often induced by proinflammatory stimuli such as lipopolysaccharide, TNF, or IL1 SH3D21 while the exact function of this protein remains unknown, due to the presence of three SH3 domains, it has been implicated in protein-protein interactions CDKN1C Cyclin-dependent kinase inhibitor 1C (p57, KIP2), also known as CDKN1C; negative regulator of cell proliferation FAM46C family with sequence similarity 46, member C; unknown function CHAD chondroadherin PLAU urokinase-type plasminogen activator FOXJ1 Forkhead box protein J1; transcription factor involved in ciliogenesis HIST1H3D histone SLC5A3 Sodium/myo-inositol cotransporter; expression of the myo-inositol transport protein is regulated by osmotic stress Human up-regulated 23 h p.i. Continued on next page 10

Supplementary Table 1 – continued from previous page Gene Function PMID

ANXA3 Annexin A3; inhibitor of phospholipase A2; also possesses anti-coagulant properties 25344230 CXCL5 involved in neutrophil activation 10095777 ANKRD1 may also be involved in the myofibrillar stretch-sensor system 22808421 ALPK3 kinase; plays a role in cardiomyocyte differentiation (similarity) 11418590 RBM24 plays a role in myogenic differentiation HSPB8 belongs to the superfamily of small heat-shock proteins; appears to be involved in 23056924 regulation of cell proliferation, apoptosis, and carcinogenesis, and mutations in this gene have been associated with different neuromuscular diseases CREB5 CAMP reponsive element binding; transcription factor BACH2 BTB And CNC Homology 1; transcriptional regulator that acts as repressor or activa- 25355872 tor 24968937 DUSP1 Dual specifity phosphatase CYR61 see above: Human up-regulated 3 h p.i. FOSL2 part of transcription factor complex AP-1 UBASH3B supress T-cell-driven inflammatory response 25047644 MYOF calcium/phospholipid-binding protein that plays a role in the plasmalemma repair mechanism of endothelial cells that permits rapid resealing of membranes disrupted by mechanical stress JUN part of transcription factor complex AP-1 LOC100653010 reported as an uncaracterized ncRNA, WITHDRAWN MAP2 -Associated Protein 2; the exact function of MAP2 is unknown but MAPs may stabilize the against depolymerization OSGIN1 Oxidative Stress Induced Growth Inhibitor; regulates the differentiation and prolifer- ation of normal cells through the regulation of cell death GDF5 member of the bone morphogenetic protein (BMP) family and the TGF-beta super- family; regulators of cell growth and differentiation in both embryonic and adult tis- sues KRT23 histone deacetylase inducible 23; related to cellular proliferation, cell cycle, 24039993 DNA replication, recombination and repair ABCC3 may act as an inducible transporter in the biliary and intestinal excretion of organic anions PRSS23 member of the trypsin family of serine proteases; may be an important ovarian pro- tease Human down-regulated 23 h p.i. MYCN N-myc proto-oncogene protein UROC1 involved in histidine catabolism, metabolizing urocanic acid to formiminoglutamic acid; known to protect the skin from ultra violet rays and is contained in human sweat AGXT Alanine-glyoxylate aminotransferase; this gene is expressed only in the liver and the 24012869 encoded protein is localized mostly in the peroxisomes, where it is involved in gly- oxylate detoxification SNAP25 Synaptosomal-associated protein 25; component of the trans-SNARE complex, which is proposed to account for the specificity of membrane fusion SPTLC3 Serine C-palmitoyltransferase; acyltransferase transferring groups other than aminoa- cyl groups FAM5C accepted name: BRINP3; bone morphogenetic Protein/Retinoic Acid Inducible Neural-Specific; inhibits neuronal cell proliferation by negative regulation of the cell cycle transition PLAC8 placenta-specific 8 Continued on next page 11

Supplementary Table 1 – continued from previous page Gene Function PMID NPTX2 member of the family of neuronal petraxins; is involved in excitatory synapse formation; plays a role in clustering of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA)-type glutamate receptors at established synapses, resulting in non-apoptotic cell death of dopaminergic nerve cells FAM40B accepted name: STRIP2, plays a role in the regulation of cell morphology and cy- toskeletal organization; required in the control of cell shape SNAP25 Synaptosomal-Associated Protein, 25kDa; t-SNARE involved in the molecular regu- 19546860 lation of neurotransmitter release; proposed to account for the specificity of membrane 12154365 fusion and to directly execute fusion by forming a tight complex that brings the synap- tic vesicle and plasma membranes together KANK4 may be involved in the control of formation by regulating polymer- ization Bat up-regulated 3 h p.i. ALB albumin; carrier protein for steroids, fatty acids, and thyroid hormones in the blood and plays a major role in stabilizing extracellular fluid volume AFP alpha-fetoprotein; binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin; only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties APOB apolipoprotein B; form lipoproteins by binding lipids HMGN5 High Mobility Group Nucleosome Binding Domain 5 (NSBP1); its target to nucleo- 19748358 somes and euchromatin; alters the compaction of cellular chromatin and that in living cells and interacs with linker histones TPRKB TP53RK Binding Protein; component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine JDP2 Jun dimerization protein 2; member of the AP-1 family of transcription factors; in- 21525011 volved in the maintenance of Epstein-Barr virus latency GKAP1 G Kinase Anchoring Protein 1; similar to the mouse cGMP-dependent protein kinase anchoring protein 42kDa; the mouse protein has been found to localize with the Golgi and recruit cGMP-dependent protein kinase I alpha to the Golgi in mouse testes MAP9 Microtubule-Associated Protein 9; involved in organization of the bipolar mitotic spin- dle; required for bipolar spindle assembly, mitosis progression and cytokinesis; may act by stabilizing interphase microtubules CCDC112 coiled-coil domain containing 112 PYCRL Pyrroline-5-Carboxylate Reductase-Like LZTFL1 Leucine Zipper Transcription Factor-Like 1; regulates ciliary localization of the BB- Some complex; together with the BBSome complex, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation; may play a role in neurite outgrowth; may have tumor suppressor function CIR1 Corepressor Interacting With RBPJ 1; may modulate splice site selection during al- ternative splicing of pre-mRNAs (by similarity); regulates transcription and acts as corepressor for RBPJ Bat down-regulated 3 h p.i. ANO1 Anoctamin 1, Calcium Activated; Calcium-activated chloride channel (CaCC) which plays a role in transepithelial anion transport and smooth muscle contraction NR4A2 Nuclear receptor subfamily 4, grup A, memer2; transcriptional regulator which is im- portant for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development; related to parkinson disease; members of the nuclear hormone receptor superfamily function as key transcriptional regulators of inflammation and proliferation in cardiovascular diseases Continued on next page 12

Supplementary Table 1 – continued from previous page Gene Function PMID NR4A3 Nuclear receptor subfamily 4, grup A, memer3; has been implicated in cell prolif- 16945922 eration, differentiation, and apoptosis; members of the nuclear hormone recep- tor superfamily function as key transcriptional regulators of inflammation and proliferation in cardiovascular diseases ZBTB3 Zinc Finger And BTB Domain Containing 3; may be involved in transcriptional regu- lation DOCK6 Dedicator Of Cytokinesis 6; acts as guanine nucleotide exchange factor (GEF) for CDC42 and RAC1 small GTPases NOP10 member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family; involved in various aspects of rRNA processing and modification ANAPC10 Anaphase promoting complex subunit 10; cell cycle-regulated E3 ubiquitin ligase 18485873 that controls progression through mitosis and the G1 phase of the cell cycle BLCAP Bladder Cancer Associated Protein; may regulate cell proliferation and coordi- 17031575 nate apoptosis and cell cycle progression via a novel mechanism independent of both p53/TP53 and NF-kappa-B PAX3 paired box (PAX) family of transcription factors; PAX3 has been identified with ear, 18787207 eye and facial development and involved in skeletal muscle differentiation Bat up-regulated 7 h p.i. STARD4 StAR-Related Lipid Transfer (START) Domain Containing 4; regulates sterol trans- 21900492 port and sensing CHAC1 ChaC glutathione-specific gamma-glutamylcyclotransferase 1; regulates a variety of downstream target genes and may enhance apoptosis SLC7A11 Sodium-independent; high-affinity exchange of anionic amino acids with high speci- ficity for anionic form of cystine and glutamate TPRKB TP53RK binding protein HMGN5 see above MAP9 Microtubule-Associated Protein 9; involved in organization of the bipolar mitotic spin- dle; required for bipolar spindle assembly, mitosis progression and cytokinesis; may act by stabilizing interphase microtubules PM20D2 peptidase M20 Domain Containing 2; metabolite repair or proofreading in carnosine 24891507 and homocarnosine synthesis HMGCR is the rate-limiting enzyme for cholesterol synthesis; 24643880 ZCWPW2 Zinc Finger; CW Type With PWWP Domain 2 USP35 Ubiquitin Specific Peptidase 35 TRIM14 induced by interferons, which are important component of resistance to pathogens and several TRIM proteins are known to be required for the restriction of infection by lentiviruses DUSP5 Dual specifity phosphatase NHSL2 unkown function; protein coding Bat down-regulated 7 h p.i. VGLL2 may act as a specific coactivator for the mammalian TEFs; may play a role in the development of skeletal muscles Continued on next page 13

Supplementary Table 1 – continued from previous page Gene Function PMID HAVCR1 Hepatitis A virus cellular receptor 1 (HAVcr-1) also known as T-cell immunoglob- 21536871 ulin and mucin domain 1 (TIM-1), plays critical roles in regulating immune cell activity especially regarding the host response to viral infection; TIM genes are also involved in host-virus interaction; as receptors for phosphatidylserine, TIM proteins bind many families of viruses [filovirus, flavivirus, New World are- navirus and alphavirus]; recently, TIM-1 has been shown to be a receptor or co- factor for Ebola virus entry; TIM-1 binds to Ebola virus glycoproteins (GP) and mediates Ebola virus cellular entry by increasing Ebola virus infectivity in poorly permissive cell lines; moreover, reducing expression of endogenous TIM-1 in highly permissive cell lines decreased Ebola virus infectivity; T-cell immunoglob- ulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus PTKS2 unkown function TGFB1 multifunctional protein that controls proliferation, differentiation and other 25710085 functions in many cell types; many cells synthesize TGFB1 and have specific re- 25740471 ceptors for it SORBS1 sorbin and SH3 domain containing 1; this gene encodes a CBL-associated protein 12690089 which functions in the signaling and stimulation of insulin NOP10 member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family; component of the telomerase complex ANO1 plays a role in transepithelial anion transport and smooth muscle contraction IRX5 Iroquois Homeobox 5; establishes the cardiac repolarization gradient by its repressive actions on the KCND2 potassium-channel gene; required for retinal cone bipolar cell differentiation NR4A3 the neuron-derived orphan receptor 1 (NOR1) also known as NR4A3; nuclear recep- tor family of intracellular transcription factors; plays a central regulatory role in cell proliferation, differentiation, metabolism and apoptosis OSR1 plays a role in the regulation of embryonic heart and urogenital development CYP1B1 Cytochrome P450 1B1 UBE2C Ubiquitin-conjugating enzyme E2 C TIAM2 T-Cell Lymphoma Invasion And Metastasis 2; modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities HNF1B shown to function in nephron development and regulates development of the embry- onic pancreas Bat up-regulated 23 h p.i. HLF Hepatic Leukemia Factor; promoted resistanceto cell death 23415677 TEC Non-receptor tyrosine kinase that contributes to signaling from many receptors and 24722985 participates as a signal transducer in multiple downstream pathways, including regu- lation of the actin cytoskeleton MAP3K5 Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein 12878192 kinase kinase kinase 5 (MAP3K5); MAP kinase kinase kinase, activates JNK and p38 NHSL1 Nance-Horan syndrome (NHS); the NHS gene forms a new gene family with a closely related novel gene NHS-Like1 ARHGAP27 may pay a role in clathrin-mediated endocytosis EMP1 Epithelial Membrane protein1; tomor-associated glycoprotein 8996089 ETV4 ETS translocation variant 4 BAIAP2L1 involved in signal transduction pathways that link deformation of the plasma mem- brane and remodeling of the actin cytoskeleton STK17B serine/threonine kinase 17b FRY plays a crucial role in the structural integrity of mitotic centrosomes and in the main- 25740997 tenance of spindle bipolarity Continued on next page 14

Supplementary Table 1 – continued from previous page Gene Function PMID GALNT6 Polypeptide N-acetylgalactosaminyltransferase 6 GFOD1 Glucose-Fructose Oxidoreductase Domain-Containing Protein 1; related to attention 18821565 deficit hyperactivity disorder UBASH3B Promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface SPSB1 Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5- SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquiti- nation and subsequent proteasomal degradation of target proteins Bat down-regulated 23 h p.i. HIST1H2B6 histone HIST1H2B histone HIST1H1C histone CDH6 Cadherins are calcium-dependent cell adhesion proteins; they preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus con- tribute to the sorting of heterogeneous cell types SLC2A12 Solute carrier family 2; facilitated glucose transporter member 1 NHSL2 see above SOX8/9/10 family of transcription factors; cell development RPL28 Ribosomal Protein L28; component of the 60S ribosomal subunit NPR3 Natriuretic peptide receptor3; regulate blood volume and pressure, pulmonary 23493048 hypertension, and cardiac function as well as some metabolic and growth pro- cesses FDXR see above TCP11L2 t-complex 11; testis-specific-like 2 MCF2L Guanine nucleotide exchange factor that potentially links pathways that signal through RAC1, RHOA and CDC42 SLC40A1 may be involved in iron export from duodenal epithelial cell and also in transfer of 22249207 iron between maternal and fetal circulation SESN3 member of the sestrin family of stress-induced proteins; the protein is required for normal regulation of blood glucose, insulin resistance and plays a role in lipid storage in obesity ATF5 transcription factor WDR60 this gene encodes a member of the WD repeat protein family; WD repeats are min- imally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) and may facilitate the formation of heterotrimeric or multiprotein complexes MYLIP Regulatory Light Chain Interacting Protein; E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8 FLRT2 may function in cell adhesion and/or receptor signalling ID4 inhibitor of DNA binding 4; dominant negative helix-loop-helix; transcription factor, which can act as tumor supressor but lack DNA binding activity DLEC1 unkown function; aberrant transcription of this gene may be involved in carcinogene- sis of the lung, esophagus, and kidney 15

Literature Cited Kim, S.-M. et al. Coxsackievirus B3 infection induces CYR61 activation via JNK to mediate cell death. Journal of virology 78, 13479–13488 (2004). Kurozumi, K. et al. Oncolytic HSV-1 infection of tumors induces angiogenesis and upregulates CYR61. Molecular Therapy 16, 1382–1391 (2008). Schoggins, J. W. et al. A diverse range of gene products are effectors of the type i interferon antiviral response. Nature 472, 481–485 (2011).