Entry
Name
Human cytomegalovirus infection - Rattus norvegicus (rat)
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
rno05163 Human cytomegalovirus infection
Ortholog table
Organism
Rattus norvegicus (rat) [GN:
rno ]
Gene
25267 Pdgfra; platelet-derived growth factor receptor alpha precursor [KO:K04363 ] [EC:2.7.10.1 ]
85243 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
170911 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
366508 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
134484121 LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922 ] [EC:2.7.1.153 ]
25513 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
60664 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
29741 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
116636 Eif4ebp1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
81736 Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580 ]
81504 Grb2; growth factor receptor-bound protein 2 [KO:K04364 ]
367858 Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833 ]
58960 Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369 ] [EC:2.7.12.2 ]
314436 Elk1; ETS domain-containing protein Elk-1 [KO:K04375 ]
296456 Itgav; integrin alpha-V isoform 1 precursor [KO:K06487 ]
363875 Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392 ]
366957 Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860 ]
688319 Rac3; ras-related C3 botulinum toxin substrate 3 [KO:K07861 ]
297173 RSA-14-44; ras homolog gene family, member A [KO:K04513 ]
498840 Sting1; stimulator of interferon genes protein [KO:K12654 ]
298213 Ifna2; interferon alpha family, gene 2 precursor [KO:K05414 ]
690894 Ifna1; interferon alpha family, gene 5 precursor [KO:K05414 ]
502961 Ifna4l2; similar to Interferon alpha-1 precursor [KO:K05414 ]
500491 Ifna16l1; interferon, alpha 16-like 1 precursor [KO:K05414 ]
502959 Ifna1l1; similar to put. precursor MuIFN-alpha 5 precursor [KO:K05414 ]
25625 Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158 ]
246756 Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
25663 Il1r1; interleukin-1 receptor type 1 precursor [KO:K04386 ]
287562 Ccl12; C-C motif chemokine ligand 12 precursor [KO:K14624 ]
24770 Ccl2; C-C motif chemokine 2 precursor [KO:K14624 ]
81780 Ccl5; C-C motif chemokine 5 precursor [KO:K12499 ]
24400 Gnb1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536 ]
81667 Gnb2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537 ]
60449 Gnb3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825 ]
294962 Gnb4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538 ]
83579 Gnb5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539 ]
80850 Gng2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826 ]
114117 Gng3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540 ]
114118 Gng4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541 ]
79218 Gng5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
58979 Gng7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
245986 Gng8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544 ]
114119 Gng10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
64199 Gng11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
114120 Gng12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
685513 Gng14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347 ]
685451 Gng13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547 ]
680149 Gngt1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548 ]
690825 Gngt2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549 ]
81666 Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
81662 Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
24654 Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858 ] [EC:3.1.4.11 ]
29322 Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858 ] [EC:3.1.4.11 ]
85240 Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858 ] [EC:3.1.4.11 ]
25031 Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858 ] [EC:3.1.4.11 ]
25262 Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958 ]
81678 Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
25679 Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
24675 Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348 ] [EC:3.1.3.16 ]
171378 Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348 ] [EC:3.1.3.16 ]
100361818 Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform 1 [KO:K04446 ]
311658 Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332 ]
361400 Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333 ]
305897 Nfatc4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334 ]
25686 Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
25643 Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630 ]
81664 Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
50664 Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform B [KO:K04534 ]
25542 Ccl3; C-C motif chemokine 3 precursor [KO:K05408 ]
81663 Gna12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346 ]
303634 Gna13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
60323 Arhgef1; rho guanine nucleotide exchange factor 1 [KO:K12330 ]
78966 Arhgef11; rho guanine nucleotide exchange factor 11 [KO:K12331 ]
367072 Arhgef12; rho guanine nucleotide exchange factor 12 [KO:K07532 ]
25637 Ptger1; prostaglandin E2 receptor EP1 subtype [KO:K04258 ]
81752 Ptger2; prostaglandin E2 receptor EP2 subtype [KO:K04259 ]
24929 Ptger3; prostaglandin E2 receptor EP3 subtype [KO:K04260 ]
84023 Ptger4; prostaglandin E2 receptor EP4 subtype [KO:K04261 ]
24896 Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632 ]
24499 Il6r; interleukin-6 receptor subunit alpha precursor [KO:K05055 ]
25125 Stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
83785 Vegfa; vascular endothelial growth factor A isoform 6 precursor [KO:K05448 ]
81646 Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870 ]
81647 Atf2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
79255 Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
310616 Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048 ]
362165 Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
362339 Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
314638 Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
500131 Creb5; cyclic AMP-responsive element-binding protein 5 [KO:K09047 ]
406169 Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
24772 Cxcl12; stromal cell-derived factor 1 isoform beta precursor [KO:K10031 ]
60628 Cxcr4; C-X-C chemokine receptor type 4 [KO:K04189 ]
25414 Bcar1; breast cancer anti-estrogen resistance protein 1 isoform 3 [KO:K05726 ]
117539 Il10ra; interleukin-10 receptor subunit alpha precursor [KO:K05134 ]
304091 Il10rb; interleukin-10 receptor subunit beta precursor [KO:K05135 ]
29385 Cxcr2; C-X-C chemokine receptor type 2 [KO:K05050 ]
301088 Ccr1l1; C-C chemokine receptor 1-like protein 1 [KO:K04176 ]
24747 RT1-M3-1; RT1 class Ib, locus M3-1 precursor [KO:K06751 ]
24973 RT1-A1; RT1 class Ia, locus A1 precursor [KO:K06751 ]
24974 RT1-A2; RT1 class Ia, locus A2 precursor [KO:K06751 ]
24988 RT1-M2; RT1 class Ib, locus M2 precursor [KO:K06751 ]
294213 RT1-M1-4; RT1 class I, locus M1, gene 4 precursor [KO:K06751 ]
309600 RT1-CE12; RT1 class I, locus CE12 precursor [KO:K06751 ]
309603 RT1-CE1; RT1 class I, locus CE1 precursor [KO:K06751 ]
309607 RT1-CE5; RT1 class I, locus CE5 isoform 1 precursor [KO:K06751 ]
361787 RT1-T24-1; RT1 class I, locus T24, gene 1 isoform 1 [KO:K06751 ]
365527 RT1-M6-2; RT1 class I, locus M6, gene 2 precursor [KO:K06751 ]
368153 RT1-CE7; RT1 class I, locus CE7 precursor [KO:K06751 ]
414779 RT1-CE2; RT1 class I, locus CE2 precursor [KO:K06751 ]
414783 RT1-CE4; RT1 class I, locus CE4 precursor [KO:K06751 ]
414784 RT1-T24-4; RT1 class I, locus T24, gene 4 [KO:K06751 ]
414785 RT1-M6-1; RT1 class I, locus M6, gene 1 precursor [KO:K06751 ]
414786 RT1-M1-2; RT1 class I, locus M1, gene 2 precursor [KO:K06751 ]
414789 RT1-CE15; RT1 class I, locus CE15 precursor [KO:K06751 ]
414790 RT1-CE13; RT1 class I, locus CE13 precursor [KO:K06751 ]
414791 RT1-CE11; RT1 class I, locus CE11 precursor [KO:K06751 ]
414792 RT1-CE10; RT1 class I, locus CE10 precursor [KO:K06751 ]
414793 RT1-CE3; RT1 class I, locus CE3 precursor [KO:K06751 ]
414819 RT1-CE16; RT1 class I, locus CE16 precursor [KO:K06751 ]
406194 RT1-T18; RT1 class Ib, locus T18 precursor [KO:K06751 ]
414788 RT1-T24-3; RT1 class I, locus T24, gene 3 [KO:K06751 ]
680842 RT1-M1-5; RT1 class I, M1, gene 5 precursor [KO:K06751 ]
102546590 H2-M10.6l; patr class I histocompatibility antigen, A-126 alpha chain-like [KO:K06751 ]
499400 RT1-M5; RT1 class Ib, locus M5 isoform 2 precursor [KO:K06751 ]
25163 Cdkn2a; cyclin-dependent kinase inhibitor 2A [KO:K06621 ]
114851 Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625 ]
24708 Rb1; retinoblastoma-associated protein [KO:K06618 ]
684111 E2f2; transcription factor E2F2 isoform X2 [KO:K09389 ]
25385 Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
246097 Fas; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390 ]
266610 Fadd; FAS-associated death domain protein [KO:K02373 ]
64625 Bid; BH3-interacting domain death agonist [KO:K04726 ]
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
rno04612 Antigen processing and presentation
rno04810 Regulation of actin cytoskeleton
KO pathway
LinkDB
All DBs