Entry
Name
Human cytomegalovirus infection - Camelus dromedarius (Arabian camel)
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
cdk05163 Human cytomegalovirus infection
Ortholog table
Organism
Camelus dromedarius (Arabian camel) [GN:
cdk ]
Gene
105086305 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
105107003 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
105085928 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
105084758 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
105101867 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
105092913 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649 ]
105089940 EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
105089560 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
105091467 SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099 ]
105101582 RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860 ]
105102215 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
105098117 STING1; stimulator of interferon response cGAMP interactor 1 [KO:K12654 ]
105098228 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158 ]
105088459 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
105105557 GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536 ]
105088562 GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537 ]
105098202 GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825 ]
105085924 GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538 ]
105086620 GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539 ]
105091500 GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540 ]
105088827 GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541 ]
116156024 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4-like [KO:K04541 ]
105095042 GNG5; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
116148370 GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
105104028 GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 isoform X5 [KO:K04544 ]
116152527 GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
105088740 GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
105104066 GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 isoform X3 [KO:K04347 ]
116156911 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
105098452 GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547 ]
105088741 GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548 ]
116157907 GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 isoform X1 [KO:K04549 ]
105087414 guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634 ]
105106041 GNA11; LOW QUALITY PROTEIN: guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
105101292 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
105101500 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
105101545 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X4 [KO:K05858 ] [EC:3.1.4.11 ]
105096910 PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
105093156 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958 ]
105101373 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960 ]
105105602 CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183 ]
105102643 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105092463 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105089593 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105103850 NFATC1; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
105105081 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X4 [KO:K17332 ]
105088479 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
105102434 NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334 ]
105087520 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
105085647 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630 ]
105100375 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
105096168 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
105086681 GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346 ]
105085708 GNA13; LOW QUALITY PROTEIN: guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
105105625 ARHGEF11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331 ]
105090126 ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532 ]
116148424 PTGER1; LOW QUALITY PROTEIN: prostaglandin E2 receptor EP1 subtype [KO:K04258 ]
105091422 PTGER2; prostaglandin E2 receptor EP2 subtype isoform X1 [KO:K04259 ]
105096638 PTGER3; prostaglandin E2 receptor EP3 subtype isoform X3 [KO:K04260 ]
105095656 LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632 ]
105090458 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
105093562 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870 ]
105097571 ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
105091928 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
105089327 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
105106926 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
105105303 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
105091622 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
105102288 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
105095833 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
105090854 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
105085072 BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726 ]
105089870 IL10RB; interleukin-10 receptor subunit beta isoform X1 [KO:K05135 ]
105087509 BOLA class I histocompatibility antigen, alpha chain BL3-7 isoform X1 [KO:K06751 ]
105087478 patr class I histocompatibility antigen, B-1 alpha chain isoform X1 [KO:K06751 ]
105087511 LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751 ]
116147754 LOW QUALITY PROTEIN: saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751 ]
105104206 H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751 ]
116152169 class I histocompatibility antigen, Gogo-B*0201 alpha chain-like [KO:K06751 ]
105101330 CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625 ]
105101803 RB1; LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618 ]
105092770 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
105102832 FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390 ]
105104389 FADD; LOW QUALITY PROTEIN: FAS-associated death domain protein [KO:K02373 ]
105100737 BID; LOW QUALITY PROTEIN: BH3-interacting domain death agonist [KO:K04726 ]
105098528 LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738 ]
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
cdk04612 Antigen processing and presentation
cdk04810 Regulation of actin cytoskeleton
KO pathway
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