Entry
Name
Human cytomegalovirus infection
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
BRITE hierarchy
Pathway map
ko05163 Human cytomegalovirus infection
Ortholog table
Disease
H00368 Cytomegalovirus infection
Drug
D02736 Fomivirsen sodium (USAN)
Orthology
K22773 Betaherpesvirinae envelope glycoprotein B
K22774 HCMV immediate-early protein 1
K22775 Cytomegalovirus viral transcription factor IE2
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K22776 Cytomegalovirus apoptosis inhibitor UL38
K07208 Ras homolog enriched in brain
K07205 eukaryotic translation initiation factor 4E binding protein 1
K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma
K02580 nuclear factor NF-kappa-B p105 subunit
K04735 transcription factor p65
K04364 growth factor receptor-bound protein 2
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04375 ETS domain-containing protein Elk-1
K04684 transcription factor Sp1
K22777 Cytomegalovirus envelope glycoprotein H
K22778 Cytomegalovirus envelope glycoprotein L
K04392 Ras-related C3 botulinum toxin substrate 1
K07860 Ras-related C3 botulinum toxin substrate 2
K07861 Ras-related C3 botulinum toxin substrate 3
K04513 Ras homolog gene family, member A
K12654 stimulator of interferon genes protein
K22779 Cytomegalovirus tegument protein pp71
K05411 interferon regulatory factor 3
K03156 tumor necrosis factor superfamily, member 2
K03158 tumor necrosis factor receptor superfamily member 1A
K02861 receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1 ]
K03171 tumor necrosis factor receptor type 1-associated DEATH domain protein
K09849 TNF receptor-associated factor 5
K04386 interleukin 1 receptor type I
K22780 Cytomegalovirus tegument protein UL26
K04734 NF-kappa-B inhibitor alpha
K22781 HCMV envelope protein US28
K04536 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538 guanine nucleotide-binding protein subunit beta-4
K04539 guanine nucleotide-binding protein subunit beta-5
K07826 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548 guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04634 guanine nucleotide-binding protein G(q) subunit alpha
K04635 guanine nucleotide-binding protein subunit alpha-11
K04958 inositol 1,4,5-triphosphate receptor type 1
K04959 inositol 1,4,5-triphosphate receptor type 2
K04960 inositol 1,4,5-triphosphate receptor type 3
K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K06268 serine/threonine-protein phosphatase 2B regulatory subunit
K04446 nuclear factor of activated T-cells, cytoplasmic 1
K17332 nuclear factor of activated T-cells, cytoplasmic 2
K17333 nuclear factor of activated T-cells, cytoplasmic 3
K17334 nuclear factor of activated T-cells, cytoplasmic 4
K04630 guanine nucleotide-binding protein G(i) subunit alpha
K04534 guanine nucleotide-binding protein G(o) subunit alpha
K05508 C-X3-C motif chemokine 1
K04346 guanine nucleotide-binding protein subunit alpha-12
K04639 guanine nucleotide-binding protein subunit alpha-13
K12330 Rho guanine nucleotide exchange factor 1
K12331 Rho guanine nucleotide exchange factor 11
K07532 Rho guanine nucleotide exchange factor 12
K16529 A-kinase anchor protein 13
K04258 prostaglandin E receptor 1
K04259 prostaglandin E receptor 2
K04260 prostaglandin E receptor 3
K04261 prostaglandin E receptor 4
K04632 guanine nucleotide-binding protein G(s) subunit alpha
K04503 G1/S-specific cyclin-D1
K04377 Myc proto-oncogene protein
K04692 signal transducer and activator of transcription 3
K05448 vascular endothelial growth factor A
K22782 Cytomegalovirus G-protein coupled receptor UL33
K05870 cyclic AMP-responsive element-binding protein 1
K04450 cyclic AMP-dependent transcription factor ATF-2
K04374 cyclic AMP-dependent transcription factor ATF-4
K09048 cyclic AMP-responsive element-binding protein 3
K09047 cyclic AMP-responsive element-binding protein 5
K09049 cyclic AMP-dependent transcription factor ATF-6 beta
K22783 HCMV envelope glycoprotein US27
K10031 C-X-C motif chemokine 12
K04189 C-X-C chemokine receptor type 4
K05726 breast cancer anti-estrogen resistance 1
K04438 C-crk adapter molecule crk
K21533 Herpesviridae/Poxviridae viral interleukin 10
K05134 interleukin 10 receptor alpha
K05135 interleukin 10 receptor beta
K05050 C-X-C chemokine receptor type 2
K22784 HCMV glycoprotein UL22A
K04176 C-C chemokine receptor type 1
K04178 C-C chemokine receptor type 3
K04180 C-C chemokine receptor type 5
K22785 HCMV membrane glycoprotein US6
K05653 ATP-binding cassette, subfamily B (MDR/TAP), member 2 [EC:7.4.2.14 ]
K05654 ATP-binding cassette, subfamily B (MDR/TAP), member 3 [EC:7.4.2.14 ]
K08058 TAP binding protein (tapasin)
K21050 HCMV unique short US2 glycoprotein
K22786 HCMV membrane glycoprotein US11
K22787 HCMV membrane glycoprotein US3
K21051 HCMV unique short US10 glycoprotein
K06621 cyclin-dependent kinase inhibitor 2A
K06625 cyclin-dependent kinase inhibitor 1A
K06618 retinoblastoma-associated protein
K17454 transcription factor E2F1
K09389 transcription factor E2F2
K06620 transcription factor E2F3
K04389 tumor necrosis factor ligand superfamily member 6
K04390 tumor necrosis factor receptor superfamily member 6
K02373 FAS-associated death domain protein
K22788 Cytomegalovirus viral inhibitor of caspase-8-induced apoptosis
K04726 BH3 interacting domain death agonist
K02159 apoptosis regulator BAX
K14021 Bcl-2 homologous antagonist/killer
K22789 UL37 HCMV immediate early glycoprotein
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Michaelis M, Doerr HW, Cinatl J
Title
The story of human cytomegalovirus and cancer: increasing evidence and open questions.
Journal
Reference
Authors
Roy S, Arav-Boger R
Title
New cell-signaling pathways for controlling cytomegalovirus replication.
Journal
Reference
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
Reference
Authors
Evers DL, Wang X, Huang ES
Title
Cellular stress and signal transduction responses to human cytomegalovirus infection.
Journal
Reference
Authors
Murray MJ, Peters NE, Reeves MB
Title
Navigating the Host Cell Response during Entry into Sites of Latent Cytomegalovirus Infection.
Journal
Reference
Authors
Campadelli-Fiume G, Collins-McMillen D, Gianni T, Yurochko AD
Title
Integrins as Herpesvirus Receptors and Mediators of the Host Signalosome.
Journal
Reference
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
Reference
Authors
Hancock MH, Nelson JA
Title
Modulation of the NFkappab Signalling Pathway by Human Cytomegalovirus.
Journal
Virology (Hyderabad) 1:104 (2017)
Reference
Authors
Rahman MM, McFadden G
Title
Modulation of NF-kappaB signalling by microbial pathogens.
Journal
Reference
Authors
Zhang J, Feng H, Xu S, Feng P
Title
Hijacking GPCRs by viral pathogens and tumor.
Journal
Reference
Authors
Lee S, Chung YH, Lee C
Title
US28, a Virally-Encoded GPCR as an Antiviral Target for Human Cytomegalovirus Infection.
Journal
Reference
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
Reference
Authors
Couty JP, Gershengorn MC
Title
G-protein-coupled receptors encoded by human herpesviruses.
Journal
Reference
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
Reference
Authors
Vischer HF, Siderius M, Leurs R, Smit MJ
Title
Herpesvirus-encoded GPCRs: neglected players in inflammatory and proliferative diseases?
Journal
Reference
Authors
Slinger E, Langemeijer E, Siderius M, Vischer HF, Smit MJ
Title
Herpesvirus-encoded GPCRs rewire cellular signaling.
Journal
Reference
Authors
Murphy PM
Title
Viral exploitation and subversion of the immune system through chemokine mimicry.
Journal
Reference
Authors
Vischer HF, Leurs R, Smit MJ
Title
HCMV-encoded G-protein-coupled receptors as constitutively active modulators of cellular signaling networks.
Journal
Reference
Authors
de Munnik SM, Smit MJ, Leurs R, Vischer HF
Title
Modulation of cellular signaling by herpesvirus-encoded G protein-coupled receptors.
Journal
Reference
Authors
Michelson S
Title
Consequences of human cytomegalovirus mimicry.
Journal
Reference
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
Reference
Authors
Busillo JM, Benovic JL
Title
Regulation of CXCR4 signaling.
Journal
Reference
Authors
Noriega V, Redmann V, Gardner T, Tortorella D
Title
Diverse immune evasion strategies by human cytomegalovirus.
Journal
Reference
Authors
Loureiro J, Ploegh HL
Title
Antigen presentation and the ubiquitin-proteasome system in host-pathogen interactions.
Journal
Reference
Authors
Fortunato EA, McElroy AK, Sanchez I, Spector DH
Title
Exploitation of cellular signaling and regulatory pathways by human cytomegalovirus.
Journal
Reference
Authors
Cinatl J Jr, Scholz M, Doerr HW
Title
Role of tumor cell immune escape mechanisms in cytomegalovirus-mediated oncomodulation.
Journal
Reference
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
Reference
Authors
Castillo JP, Kowalik TF
Title
Human cytomegalovirus immediate early proteins and cell growth control.
Journal
Reference
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
Reference
Authors
Brune W
Title
Inhibition of programmed cell death by cytomegaloviruses.
Journal
Reference
Authors
Brune W, Andoniou CE
Title
Die Another Day: Inhibition of Cell Death Pathways by Cytomegalovirus.
Journal
Reference
Authors
Yamin R, Lecker LSM, Weisblum Y, Vitenshtein A, Le-Trilling VTK, Wolf DG, Mandelboim O
Title
HCMV vCXCL1 Binds Several Chemokine Receptors and Preferentially Attracts Neutrophils over NK Cells by Interacting with CXCR2.
Journal
Reference
Authors
Wang X, Sanchez J, Stone MJ, Payne RJ
Title
Sulfation of the Human Cytomegalovirus Protein UL22A Enhances Binding to the Chemokine RANTES.
Journal
Related pathway
ko00590 Arachidonic acid metabolism
ko04064 NF-kappa B signaling pathway
ko04612 Antigen processing and presentation
ko04623 Cytosolic DNA-sensing pathway
ko04810 Regulation of actin cytoskeleton
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