KEGG PATHWAY: ocu05163

PATHWAY: ocu05163

Entry

ocu05163                    Pathway

Name

Human cytomegalovirus infection - Oryctolagus cuniculus (rabbit)

Description

Human cytomegalovirus (HCMV) is an enveloped, double-stranded DNA virus that is a member of beta-herpesvirus family. HCMV is best known for causing significant morbidity and mortality in immunocompromised populations. As with other herpesviruses, HCMV gB and gH/gL envelope glycoproteins are essential for virus entry. HCMV gB could activate the PDGFRA, and induce activation of the oncogenic PI3-K/AKT pathway. Though it is unlikely that HCMV by itself can act as an oncogenic factor, HCMV may have an oncomodulatory role, to catalyze an oncogenic process that has already been initiated. US28, one of the four HCMV-encoded vGPCRs (US27, US28, UL33 and UL78), also has a specific role in the oncomodulatory properties. In addition, HCMV has developed numerous mechanisms for manipulating the host immune system. The virally encoded US2, US3, US6 and US11 gene products all interfere with major histocompatibility complex (MHC) class I antigen presentation. HCMV encodes several immediate early (IE) antiapoptotic proteins (IE1, IE2, vMIA and vICA). These proteins might avoid immune clearance of infected tumor cells by cytotoxic lymphocytes and NK cells.

Class

Human Diseases; Infectious disease: viral

Pathway map

ocu05163

Human cytomegalovirus infection

Disease

H00368

Cytomegalovirus infection

Organism

Oryctolagus cuniculus (rabbit) [GN:ocu]

Gene

100008609

FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]

100008680

[KO:K04258]

100008733

IL6; interleukin-6 precursor [KO:K05405]

100008735

ITGB3; integrin beta-3 precursor [KO:K06493]

100008806

[KO:K04361] [EC:2.7.10.1]

100008815

PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]

100008840

CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]

100008859

[KO:K17333]

100008899

[KO:K05448]

100008904

[KO:K04632]

100008939

[KO:K04960]

100008941

GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]

100008956

[KO:K06487]

100008984

CCL4; C-C motif chemokine 4 precursor [KO:K12964]

100008990

IL1B; interleukin-1 beta precursor [KO:K04519]

100009039

[KO:K02089] [EC:2.7.11.22]

100009040

[KO:K02091] [EC:2.7.11.22]

100009050

CALR; calreticulin precursor [KO:K08057]

100009081

PTGER4; prostaglandin E2 receptor EP4 subtype [KO:K04261]

100009088

TNF; tumor necrosis factor precursor [KO:K03156]

100009102

PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]

100009129

CXCL8; interleukin-8 precursor [KO:K10030]

100009130

CCL2; C-C motif chemokine 2 precursor [KO:K14624]

100009201

[KO:K08042] [EC:4.6.1.1]

100009220

ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]

100009248

PTGS2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]

100009260

RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]

100009292

TP53; cellular tumor antigen p53 [KO:K04451]

100009315

ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]

100009316

MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]

100009369

PTGER2; prostaglandin E2 receptor EP2 subtype [KO:K04259]

100009389

PTGER3; prostaglandin E2 receptor EP3 subtype isoform 1 [KO:K04260]

100009423

PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]

100009487

PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]

100009505

[KO:K04958]

100037719

PRKCB; protein kinase C beta type isoform I [KO:K19662] [EC:2.7.11.13]

100037720

PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]

100101579

CCR5; C-C chemokine receptor type 5 [KO:K04180]

100101592

[KO:K04399] [EC:3.4.22.62]

100125985

[KO:K02105]

100189557

CCR3; C-C chemokine receptor type 3 [KO:K04178]

100327265

MYC; myc proto-oncogene protein [KO:K04377]

100328627

CXCR2; C-X-C chemokine receptor type 2 [KO:K05050]

100328685

PDIA3; protein disulfide-isomerase A3 precursor [KO:K08056] [EC:5.3.4.1]

100328905

IKBKG; NF-kappa-B essential modulator [KO:K07210]

100328940

CCR1; C-C chemokine receptor type 1 [KO:K04176]

100328967

[KO:K06751]

100337783

[KO:K04536]

100337815

[KO:K12331]

100337822

[KO:K00922] [EC:2.7.1.153]

100337882

[KO:K08048] [EC:4.6.1.1]

100337888

[KO:K03171]

100338332

[KO:K04538]

100338351

[KO:K05135]

100338391

[KO:K04630]

100338695

[KO:K07206]

100338822

[KO:K06751]

100338850

[KO:K07205]

100339066

[KO:K04630]

100339383

[KO:K04374]

100339821

[KO:K06751]

100339873

[KO:K04392]

100340005

[KO:K09849]

100340118

[KO:K07532]

100340625

[KO:K06621]

100340661

[KO:K04513]

100340719

[KO:K04634]

100340877

[KO:K08049] [EC:4.6.1.1]

100340952

[KO:K04375]

100341050

[KO:K08738]

100341175

[KO:K08738]

100341512

[KO:K05858] [EC:3.1.4.11]

100341515

[KO:K08738]

100341599

[KO:K05704] [EC:2.7.10.2]

100341695

[KO:K04441] [EC:2.7.11.24]

100342046

[KO:K14021]

100342201

[KO:K04546]

100342212

[KO:K04345] [EC:2.7.11.11]

100342283

[KO:K04534]

100342327

[KO:K04438]

100342358

[KO:K05871] [EC:2.7.10.2]

100342409

[KO:K16529]

100342450

[KO:K04548]

100342500

[KO:K04364]

100342852

[KO:K04456] [EC:2.7.11.1]

100342931

[KO:K05415]

100343006

[KO:K04363] [EC:2.7.10.1]

100343130

[KO:K09048]

100343368

[KO:K04513]

100343680

[KO:K04513]

100343958

[KO:K08043] [EC:4.6.1.1]

100344073

[KO:K04389]

100344161

[KO:K04441] [EC:2.7.11.24]

100344241

[KO:K07828]

100344533

[KO:K06268]

100345181

[KO:K00922] [EC:2.7.1.153]

100345250

[KO:K02649]

100345475

[KO:K09048]

100345526

[KO:K02183]

100346106

[KO:K03158]

100346186

[KO:K05508]

100346189

[KO:K04189]

100346323

[KO:K04632]

100346379

[KO:K09389]

100346391

[KO:K03099]

100346625

[KO:K07825]

100346742

[KO:K08044] [EC:4.6.1.1]

100346837

[KO:K17388] [EC:2.7.11.39]

100346856

[KO:K04513]

100347003

[KO:K17334]

100347293

[KO:K04346]

100347345

[KO:K04371] [EC:2.7.11.24]

100347407

[KO:K04366] [EC:2.7.11.1]

100347455

[KO:K05725] [EC:2.7.10.2]

100347487

[KO:K07827]

100347752

[KO:K05055]

100347856

[KO:K02183]

100348266

[KO:K12499]

100348350

[KO:K04540]

100348477

[KO:K04398] [EC:3.4.22.61]

100348489

[KO:K06625]

100348492

[KO:K07208]

100348561

[KO:K04371] [EC:2.7.11.24]

100348663

[KO:K00922] [EC:2.7.1.153]

100348672

[KO:K05858] [EC:3.1.4.11]

100348776

[KO:K05408]

100348778

[KO:K04692]

100348842

[KO:K03083] [EC:2.7.11.26]

100348967

[KO:K04513]

100348995

[KO:K06751]

100349085

[KO:K06751]

100349135

STING1; stimulator of interferon genes protein isoform X1 [KO:K12654]

100349155

[KO:K05653] [EC:7.4.2.14]

100349247

[KO:K06751]

100349407

CGAS; cyclic GMP-AMP synthase isoform X1 [KO:K17834] [EC:2.7.7.86]

100349426

[KO:K02580]

100349757

[KO:K06751]

100350107

[KO:K02183]

100350323

[KO:K05726]

100350395

[KO:K05858] [EC:3.1.4.11]

100350417

[KO:K08057]

100350614

[KO:K04441] [EC:2.7.11.24]

100350679

[KO:K08055]

100351037

[KO:K08738]

100351317

[KO:K04684]

100351640

[KO:K07207]

100351666

[KO:K05654] [EC:7.4.2.14]

100351999

[KO:K05870]

100352378

[KO:K04446]

100352392

CALM2; calmodulin [KO:K02183]

100352594

[KO:K11217] [EC:2.7.10.2]

100352794

[KO:K04639]

100352905

[KO:K04386]

100352954

[KO:K07826]

100352965

[KO:K02861] [EC:2.7.11.1]

100353173

[KO:K06620]

100353305

[KO:K05760]

100353390

[KO:K05414]

100353673

[KO:K08738]

100353706

[KO:K04456] [EC:2.7.11.1]

100353824

[KO:K17332]

100354468

[KO:K08738]

100354611

[KO:K06751]

100354654

[KO:K05414]

100354694

[KO:K08058]

100354724

[KO:K08738]

100354902

[KO:K05134]

100354905

[KO:K02183]

100354934

[KO:K08046] [EC:4.6.1.1]

100355084

[KO:K08738]

100355230

[KO:K04433] [EC:2.7.12.2]

100355367

[KO:K04450]

100355380

[KO:K06751]

100355417

[KO:K04544]

100355669

[KO:K05414]

100355675

[KO:K02159]

100355888

[KO:K04467] [EC:2.7.11.10]

100355912

[KO:K05414]

100355991

[KO:K04726]

100356164

[KO:K07203] [EC:2.7.11.1]

100356245

[KO:K04348] [EC:3.1.3.16]

100356250

[KO:K04513]

100356371

RLA-A3; MHC class I antigen-like precursor [KO:K06751]

100356401

[KO:K07209] [EC:2.7.11.10]

100356419

[KO:K05414]

100356520

[KO:K07860]

100356615

[KO:K03099]

100356678

[KO:K05414]

100356799

[KO:K04537]

100356806

[KO:K04959]

100356957

[KO:K17454]

100357194

[KO:K05414]

100357329

[KO:K08738]

100357341

[KO:K04734]

100357357

[KO:K08047] [EC:4.6.1.1]

100357431

[KO:K06618]

100357483

[KO:K09047]

100357489

[KO:K09049]

100357708

[KO:K05414]

100357840

[KO:K08738]

100357841

[KO:K02649]

100357876

[KO:K09048]

100358175

[KO:K09048]

100358771

[KO:K05410] [EC:2.7.11.10]

100359147

[KO:K04630]

103345165

[KO:K02183]

103345545

[KO:K10031]

103346035

[KO:K04441] [EC:2.7.11.24]

103346571

[KO:K05411]

103347035

[KO:K08041] [EC:4.6.1.1]

103347536

[KO:K05858] [EC:3.1.4.11]

103347573

[KO:K12330]

103347723

[KO:K08738]

103350153

[KO:K04347]

103350926

[KO:K04541]

108175836

[KO:K08738]

108176185

GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]

108177128

[KO:K04545]

108177422

[KO:K08738]

108178480

[KO:K04542]

108178552

[KO:K04549]

108178730

[KO:K08738]

127483320

[KO:K08738]

127484730

[KO:K04688] [EC:2.7.11.1]

127485184

[KO:K04735]

127486116

[KO:K04456] [EC:2.7.11.1]

127486605

[KO:K02833]

127489175

[KO:K17454]

127489236

[KO:K07827]

127489280

[KO:K04536]

127489461

[KO:K04368] [EC:2.7.12.2]

127489660

[KO:K04513]

127489712

[KO:K04547]

127493063

[KO:K09049]

Compound

C00076

Calcium cation

C00165

Diacylglycerol

C00584

Prostaglandin E2

C01245

D-myo-Inositol 1,4,5-trisphosphate

C05981

Phosphatidylinositol-3,4,5-trisphosphate

C20640

Cyclic GMP-AMP

Reference

PMID:19107226

Authors

Michaelis M, Doerr HW, Cinatl J

Title

The story of human cytomegalovirus and cancer: increasing evidence and open questions.

Journal

Neoplasia 11:1-9 (2009)
DOI:10.1593/neo.81178

Reference

PMID:24839861

Authors

Roy S, Arav-Boger R

Title

New cell-signaling pathways for controlling cytomegalovirus replication.

Journal

Am J Transplant 14:1249-58 (2014)
DOI:10.1111/ajt.12725

Reference

PMID:14720582

Authors

Cinatl J, Scholz M, Kotchetkov R, Vogel JU, Doerr HW

Title

Molecular mechanisms of the modulatory effects of HCMV infection in tumor cell biology.

Journal

Trends Mol Med 10:19-23 (2004)
DOI:10.1016/j.molmed.2003.11.002

Reference

PMID:15380778

Authors

Evers DL, Wang X, Huang ES

Title

Cellular stress and signal transduction responses to human cytomegalovirus infection.

Journal

Microbes Infect 6:1084-93 (2004)
DOI:10.1016/j.micinf.2004.05.026

Reference

PMID:29547547

Authors

Murray MJ, Peters NE, Reeves MB

Title

Navigating the Host Cell Response during Entry into Sites of Latent Cytomegalovirus Infection.

Journal

Pathogens 7:E30 (2018)
DOI:10.3390/pathogens7010030

Reference

PMID:27501260

Authors

Campadelli-Fiume G, Collins-McMillen D, Gianni T, Yurochko AD

Title

Integrins as Herpesvirus Receptors and Mediators of the Host Signalosome.

Journal

Annu Rev Virol 3:215-236 (2016)
DOI:10.1146/annurev-virology-110615-035618

Reference

PMID:28132838

Authors

Fu YZ, Su S, Gao YQ, Wang PP, Huang ZF, Hu MM, Luo WW, Li S, Luo MH, Wang YY, Shu HB

Title

Human Cytomegalovirus Tegument Protein UL82 Inhibits STING-Mediated Signaling to Evade Antiviral Immunity.

Journal

Cell Host Microbe 21:231-243 (2017)
DOI:10.1016/j.chom.2017.01.001

Reference

PMID:29082387

Authors

Hancock MH, Nelson JA

Title

Modulation of the NFkappab Signalling Pathway by Human Cytomegalovirus.

Journal

Virology (Hyderabad) 1:104 (2017)

Reference

PMID:21383764

Authors

Rahman MM, McFadden G

Title

Modulation of NF-kappaB signalling by microbial pathogens.

Journal

Nat Rev Microbiol 9:291-306 (2011)
DOI:10.1038/nrmicro2539

Reference

PMID:27060663

Authors

Zhang J, Feng H, Xu S, Feng P

Title

Hijacking GPCRs by viral pathogens and tumor.

Journal

Biochem Pharmacol 114:69-81 (2016)
DOI:10.1016/j.bcp.2016.03.021

Reference

PMID:28035083

Authors

Lee S, Chung YH, Lee C

Title

US28, a Virally-Encoded GPCR as an Antiviral Target for Human Cytomegalovirus Infection.

Journal

Biomol Ther (Seoul) 25:69-79 (2017)
DOI:10.4062/biomolther.2016.208

Reference

PMID:23145028

Authors

Langemeijer EV, Slinger E, de Munnik S, Schreiber A, Maussang D, Vischer H, Verkaar F, Leurs R, Siderius M, Smit MJ

Title

Constitutive beta-catenin signaling by the viral chemokine receptor US28.

Journal

PLoS One 7:e48935 (2012)
DOI:10.1371/journal.pone.0048935

Reference

PMID:15990176

Authors

Couty JP, Gershengorn MC

Title

G-protein-coupled receptors encoded by human herpesviruses.

Journal

Trends Pharmacol Sci 26:405-11 (2005)
DOI:10.1016/j.tips.2005.06.004

Reference

PMID:25549333

Authors

Fiallos E, Judkins J, Matlaf L, Prichard M, Dittmer D, Cobbs C, Soroceanu L

Title

Human cytomegalovirus gene expression in long-term infected glioma stem cells.

Journal

PLoS One 9:e116178 (2014)
DOI:10.1371/journal.pone.0116178

Reference

PMID:24445563

Authors

Vischer HF, Siderius M, Leurs R, Smit MJ

Title

Herpesvirus-encoded GPCRs: neglected players in inflammatory and proliferative diseases?

Journal

Nat Rev Drug Discov 13:123-39 (2014)
DOI:10.1038/nrd4189

Reference

PMID:20398729

Authors

Slinger E, Langemeijer E, Siderius M, Vischer HF, Smit MJ

Title

Herpesvirus-encoded GPCRs rewire cellular signaling.

Journal

Mol Cell Endocrinol 331:179-84 (2011)
DOI:10.1016/j.mce.2010.04.007

Reference

PMID:11175803

Authors

Murphy PM

Title

Viral exploitation and subversion of the immune system through chemokine mimicry.

Journal

Nat Immunol 2:116-22 (2001)
DOI:10.1038/84214

Reference

PMID:16352349

Authors

Vischer HF, Leurs R, Smit MJ

Title

HCMV-encoded G-protein-coupled receptors as constitutively active modulators of cellular signaling networks.

Journal

Trends Pharmacol Sci 27:56-63 (2006)
DOI:10.1016/j.tips.2005.11.006

Reference

PMID:25805993

Authors

de Munnik SM, Smit MJ, Leurs R, Vischer HF

Title

Modulation of cellular signaling by herpesvirus-encoded G protein-coupled receptors.

Journal

Front Pharmacol 6:40 (2015)
DOI:10.3389/fphar.2015.00040

Reference

PMID:15172446

Authors

Michelson S

Title

Consequences of human cytomegalovirus mimicry.

Journal

Hum Immunol 65:465-75 (2004)
DOI:10.1016/j.humimm.2004.02.002

Reference

PMID:29237840

Authors

Tu CC, Arnolds KL, O'Connor CM, Spencer JV

Title

Human Cytomegalovirus UL111A and US27 Gene Products Enhance the CXCL12/CXCR4 Signaling Axis via Distinct Mechanisms.

Journal

J Virol 92:e01981-17 (2018)
DOI:10.1128/JVI.01981-17

Reference

PMID:17169327

Authors

Busillo JM, Benovic JL

Title

Regulation of CXCR4 signaling.

Journal

Biochim Biophys Acta 1768:952-63 (2007)
DOI:10.1016/j.bbamem.2006.11.002

Reference

PMID:22454101

Authors

Noriega V, Redmann V, Gardner T, Tortorella D

Title

Diverse immune evasion strategies by human cytomegalovirus.

Journal

Immunol Res 54:140-51 (2012)
DOI:10.1007/s12026-012-8304-8

Reference

PMID:17145306

Authors

Loureiro J, Ploegh HL

Title

Antigen presentation and the ubiquitin-proteasome system in host-pathogen interactions.

Journal

Adv Immunol 92:225-305 (2006)
DOI:10.1016/S0065-2776(06)92006-9

Reference

PMID:10707064

Authors

Fortunato EA, McElroy AK, Sanchez I, Spector DH

Title

Exploitation of cellular signaling and regulatory pathways by human cytomegalovirus.

Journal

Trends Microbiol 8:111-9 (2000)
DOI:10.1016/S0966-842X(00)01699-1

Reference

PMID:15389728

Authors

Cinatl J Jr, Scholz M, Doerr HW

Title

Role of tumor cell immune escape mechanisms in cytomegalovirus-mediated oncomodulation.

Journal

Med Res Rev 25:167-85 (2005)
DOI:10.1002/med.20018

Reference

PMID:14975530

Authors

Cinatl J Jr, Vogel JU, Kotchetkov R, Wilhelm Doerr H

Title

Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression.

Journal

FEMS Microbiol Rev 28:59-77 (2004)
DOI:10.1016/j.femsre.2003.07.005

Reference

PMID:12062798

Authors

Castillo JP, Kowalik TF

Title

Human cytomegalovirus immediate early proteins and cell growth control.

Journal

Gene 290:19-34 (2002)
DOI:10.1016/S0378-1119(02)00566-8

Reference

PMID:15352160

Authors

Kalejta RF

Title

Human cytomegalovirus pp71: a new viral tool to probe the mechanisms of cell cycle progression and oncogenesis controlled by the retinoblastoma family of tumor suppressors.

Journal

J Cell Biochem 93:37-45 (2004)
DOI:10.1002/jcb.20177

Reference

PMID:20969904

Authors

Brune W

Title

Inhibition of programmed cell death by cytomegaloviruses.

Journal

Virus Res 157:144-50 (2011)
DOI:10.1016/j.virusres.2010.10.012

Reference

PMID:28869497