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ABCDEF Supplementary Figure S1 01-Tube-A2 : P1 01-Tube-A3 : P1 50 50 Count Count P2(0.03%) P2(9.91%) 0 0 10 2 10 3 10 4 10 5 10 6 10 2 10 3 10 4 10 5 10 6 A FITC-A B FITC-A 01-Tube-A4 : P1 01-Tube-A5 : P1 60 50 40 Count Count 20 P2(9.44%) P2(9.73%) 0 0 10 2 10 3 10 4 10 5 10 6 10 2 10 3 10 4 10 5 10 6 C FITC-A D FITC-A 01-Tube-A8 : P1 01-Tube-A10 : P1 50 50 Count Count P2(9.80%) P2(9.22%) 0 0 10 2 10 3 10 4 10 5 10 6 10 2 10 3 10 4 10 5 10 6 E FITC-A F FITC-A Supplementary figure S1: Rate of infection of PBMC with Ab4-wt and mutant viruses. PBMC were infected with Ab4-wt or mutant viruses at an MOI of 0.1 for 24 h. Infected PBMC were sorted based on egfp expression using FACSAria (BD Bioscience) and used for transwell co-cultivation and flow chamber experiments. (A) mock infected (B) Ab4-wt, (C) Ab4∆ORF1 (D) Ab4∆ORF2 (E) Ab4∆ORF17) and (F) Ab4∆/ORF1/ORF2/ORF17 infected PBMC at 24 hrs post infection. P2 indicates percentage of egfp positive PBMC. (n=4) Pathways upregulated Pathways downregulated Infected Pathways Genes Pathways Genes population Lysosome ATPase H+ transporting V0 subunit d1 Herpesvirus CD58 molecule Adaptor related protein complex 3 mu 1 infection Proteasome 26S subunit, non-ATPase 2 subunit recombination signal binding protein for Adaptor related protein complex 3 mu 2 immunoglobulin kappa J region like subunit recombination signal binding protein for Scavenger receptor class B member 2 immunoglobulin kappa J region Ras signaling RAP1A, member of RAS oncogene family pathway Phosphoinositide-3-kinase regulatory subunit 1 Ras-related protein Rap-1A Endocytosis EH domain containing 1 Spliceosome LSM6 homolog, U6 small nuclear RNA and PBMC EH domain containing 3 mRNA degradation associated Vs RAB35, member RAS oncogene family RNA binding motif protein 22 Ab4-wt RAB5A, member RAS oncogene family Cell division cycle 40 Platelet RAP1A, member of RAS oncogene family Squamous cell carcinoma antigen recognized by activation Phosphoinositide-3-kinase regulatory T-cells 1 Leukocyte subunit 1 Chemokine RAP1A, member of RAS oncogene family transendothelial Ras-related protein Rap-1A signaling Mitogen-activated protein kinase kinase 1 migration pathway Stress induced phosphoprotein 1 Oxidative ATP synthase, H+ transporting, RNA TNFRSF1A associated via death domain phosphorylation mitochondrial F1 complex, alpha subunit 1 degradation Chromodomain helicase DNA binding protein 4 ATPase H+ transporting V0 subunit d1 LSM6 homolog, U6 small nuclear RNA and NADH:ubiquinone oxidoreductase core mRNA degradation associated subunit V1 RNA binding motif protein 22 Fatty acid Hydroxysteroid 17-beta dehydrogenase 12 Apoptosis Apoptosis inducing factor, mitochondria elongation Mitochondrial trans-2-enoyl-CoA reductase associated 1 Caspase 1, apoptosis-related cysteine peptidase Caspase 10 MALT1 paracaspase Herpesvirus CD58 molecule Chemokine RAP1A, member of RAS oncogene family infection TNFRSF1A associated via death domain signaling Mitogen-activated protein kinase kinase 1 Proteasome 26S subunit, non-ATPase 12 pathway Ras-related protein Rap-1A Recombination signal binding protein for Stress induced phosphoprotein 1 immunoglobulin kappa J region like Recombination signal binding protein for PBMC immunoglobulin kappa J region l Vs Lysosome ATPase H+ transporting V0 subunit d1 MAPK Protein phosphatase 5 catalytic subunit Ab4∆ORF17 Adaptor related protein complex 3 mu 1 signaling RAP1A, member of RAS oncogene family subunit pathway Mitogen-activated protein kinase kinase 1 Adaptor related protein complex 3 mu 2 Ras-related protein Rap-1A subunit Scavenger receptor class B member 2 Oxidative ATP synthase, H+ transporting, phosphorylation mitochondrial F1 complex, alpha subunit 1 RNA transport RNA binding motif protein 22 ATPase H+ transporting V0 subunit d1 Pre-mRNA processing factor 3 NADH:ubiquinone oxidoreductase core NOP2/Sun RNA methyltransferase family subunit V1 member 2 Protein ER membrane protein complex subunit 1 Ribosomal RNA processing 1B processing in Endoplasmic reticulum lectin 1 Spliceosome LSM6 homolog, U6 small nuclear RNA and endoplasmic Serine/threonine-protein phosphatise 6 mRNA degradation associated reticulum and Fc catalytic subunit RNA binding motif protein 22 epsilon RI Receptor-type tyrosine-protein phosphatase Cell division cycle 40 signaling epsilon Squamous cell carcinoma antigen recognized by T-cells 1 Metabolic 24-dehydrocholesterol reductase pathways T-cell immune regulator 1, ATPase H+ transporting V0 subunit a3 Acetyl-CoA acetyltransferase 2 Acyl-CoA synthetase long-chain family member 3 Adenosylhomocysteinase like 1 Adenosylhomocysteinase like 2 Branched chain amino acid transaminase 2 Ceramide synthase 2 Inositol polyphosphate-1-phosphatase Methylcrotonoyl-CoA carboxylase 1 Methylcrotonoyl-CoA carboxylase 2 Phosphatidylinositol glycan anchor biosynthesis class U Phospholipase B1 Pyruvate dehydrogenase complex component mTOR signaling 3-phosphoinositide dependent protein Metabolic ATP synthase, H+ transporting, mitochondrial F1 pathway kinase 1 pathways complex, epsilon subunit (ATP5E) Ras related GTP binding C ATPase H+ transporting V0 subunit a1 Ras related GTP binding D NADH:ubiquinone oxidoreductase core subunit Phosphatidylinositol-4,5-bisphosphate 3- V1 kinase catalytic subunit gamma Aconitase 1 PBMC Herpesvirus CD58 molecule Fucokinase Vs infection Phosphatidylinositol-4,5-bisphosphate 3- Galactosidase beta 1 Ab4∆ORF1 kinase catalytic subunit gamma Hydroxysteroid 17-beta dehydrogenase 12 Proteasome 26S subunit, non-ATPase 12 Mannosidase alpha class 2A member 1 Lysosome ATPase H+ transporting V0 subunit d1 Thymidine phosphorylase Adaptor related protein complex 3 mu 1 subunit Adaptor related protein complex 3 mu 2 subunit Scavenger receptor class B member 2 Chemokine RAP1A, member of RAS oncogene family Spliceosome LSM6 homolog, U6 small nuclear RNA and signaling Mitogen-activated protein kinase kinase 1 mRNA degradation associated pathway Ras-related protein Rap-1A RNA binding motif protein 22 Stress induced phosphoprotein 1 Cell division cycle 40 Squamous cell carcinoma antigen recognized by T-cells 1 Platelet RAP1A, member of RAS oncogene family RNA TNFRSF1A associated via death domain activation Phosphoinositide-3-kinase regulatory degradation Chromodomain helicase DNA binding protein 4 Leukocyte subunit 1 LSM6 homolog, U6 small nuclear RNA and transendothelial Ras-related protein Rap-1A mRNA degradation associated migration CD58 molecule RNA binding motif protein 22 Focal adhesion RAP1A, member of RAS oncogene family Aminoacyl- Histidyl-tRNA synthetase 2, mitochondrial and Ras signaling Phosphoinositide-3-kinase regulatory tRNA Histidyl-tRNA synthetase pathway subunit 1 biosynthesis phenylalanyl-tRNA synthetase beta subunit Ras-related protein Rap-1A Endocytosis EH domain containing 1 EH domain containing 3 RAB35, member RAS oncogene family Herpesvirus CD58 molecule Spliceosome LSM6 homolog, U6 small nuclear RNA and infection proteasome 26S subunit, non-ATPase 12 mRNA degradation associated proteasome 26S subunit, non-ATPase 2 RNA binding motif protein 22 mTOR signaling 3-phosphoinositide dependent protein Cell division cycle 40 kinase 1 Squamous cell carcinoma antigen recognized by Ras related GTP binding C T-cells 1 Ras related GTP binding D Phosphatidylinositol-4,5-bisphosphate 3- kinase catalytic subunit gamma PBMC Regulation of FYVE, RhoGEF and PH domain containing 3 RNA TNFRSF1A associated via death domain Vs actin Integrin subunit beta degradation Chromodomain helicase DNA binding protein 4 Ab4∆ORF2 cytoskeleton Phosphatidylinositol-4,5-bisphosphate 3- LSM6 homolog, U6 small nuclear RNA and kinase catalytic subunit gamma mRNA degradation associated Phosphatidylinositol-5-phosphate 4-kinase RNA binding motif protein 22 type 2 gamma Protein phosphatase 1 regulatory subunit 12A Chemokine RAP1A, member of RAS oncogene family MAPK RAP1A, member of RAS oncogene family signaling Mitogen-activated protein kinase kinase 1 signaling Interleukin 1 alpha pathway Ras-related protein Rap-1A pathway Protein phosphatase 5 catalytic subunit Stress induced phosphoprotein 1 Ras-related protein Rap-1A Ribosomal protein S6 kinase A5 Endocytosis EH domain containing 1 Spliceosome LSM6 homolog, U6 small nuclear RNA and EH domain containing 3 mRNA degradation associated RAB35, member RAS oncogene family RNA binding motif protein 22 RAB5A, member RAS oncogene family Cell division cycle 40 Herpesvirus CD58 molecule Squamous cell carcinoma antigen recognized by infection proteasome 26S subunit, non-ATPase 12 T-cells 1 proteasome 26S subunit, non-ATPase 2 Lysosome ATPase H+ transporting V0 subunit d1 MAPK RAP1A, member of RAS oncogene family Adaptor related protein complex 3 mu 1 signaling Interleukin 1 alpha subunit pathway Protein phosphatase 5 catalytic subunit Adaptor related protein complex 3 mu 2 Ras-related protein Rap-1A PBMC subunit Ribosomal protein S6 kinase A5 Vs Scavenger receptor class B member 2 Ab4∆ORF1/ Chemokine RAP1A, member of RAS oncogene family ORF2/ORF17 signaling Mitogen-activated protein kinase kinase 1 TNFRSF1A associated via death domain pathway Ras-related protein Rap-1A RNA Chromodomain helicase DNA binding protein 4 Stress induced phosphoprotein 1 degradation LSM6 homolog, U6 small nuclear RNA and T cell signaling T-cell immune regulator 1, ATPase H+ mRNA degradation associated transporting V0 subunit a3 RNA binding motif protein 22 Squamous cell carcinoma antigen recognized by T-cells 1 Phosphatidylinositol-4,5-bisphosphate 3- kinase catalytic subunit gamma Phosphatidylinositol-5-phosphate 4-kinase type 2 gamma
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