KEGG   PATHWAY: hsa04061
Entry
hsa04061                    Pathway                                
Name
Viral protein interaction with cytokine and cytokine receptor - Homo sapiens (human)
Description
Viruses have evolved diverse mechanisms to evade detection and destruction by the immune system, including copying and repurposing host cytokine and cytokine receptor genes. Viral cytokines and cytokine receptors, together with a group of structurally unique, soluble, cytokine-binding or cytokine receptor-binding proteins, represent the three major molecular strategies for subversion and modulation of the host cytokine networks mainly in large DNA viruses. Viral cytokines and cytokine receptor homologs, including other binding proteins, may activate or inhibit cytokine signaling and possibly affect different aspects of immunity.
Class
Environmental Information Processing; Signaling molecules and interaction
Pathway map
hsa04061  Viral protein interaction with cytokine and cytokine receptor
hsa04061

Network
  Element
N00350  HPV E6 to extrinsic apoptotic pathway
N00416  HCMV vIL10 to IL10-JAK-STAT signaling pathway
N00427  HCMV vCXCL to CXCR-GNB/G-PI3K-AKT signaling pathway
N00429  HCMV UL22A to CCR5-GNB/G-PLCB/G-PKC signaling pathway
N00491  HTLV-1 p12 to Jak-STAT signaling pathway
N00560  HSV gD to HVEM-NFKB signaling pathway
Drug
D03210  Ancriviroc (USAN/INN)
D06297  Vicriviroc maleate (USAN)
D06557  Aplaviroc hydrochloride (USAN)
D06670  Maraviroc (JAN/INN)
D09878  Cenicriviroc (USAN/INN)
D11399  Leronlimab (USAN/INN)
D12648  Quisovalimab (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
6352  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
6348  CCL3; C-C motif chemokine ligand 3 [KO:K05408]
6349  CCL3L1; C-C motif chemokine ligand 3 like 1 [KO:K05408]
414062  CCL3L3; C-C motif chemokine ligand 3 like 3 [KO:K05408]
6355  CCL8; C-C motif chemokine ligand 8 [KO:K16596]
6358  CCL14; C-C motif chemokine ligand 14 [KO:K21092]
6360  CCL16; C-C motif chemokine ligand 16 [KO:K21093]
6359  CCL15; C-C motif chemokine ligand 15 [KO:K05511]
6368  CCL23; C-C motif chemokine ligand 23 [KO:K05511]
6357  CCL13; C-C motif chemokine ligand 13 [KO:K16595]
6354  CCL7; C-C motif chemokine ligand 7 [KO:K05509]
6347  CCL2; C-C motif chemokine ligand 2 [KO:K14624]
10850  CCL27; C-C motif chemokine ligand 27 [KO:K16598]
6356  CCL11; C-C motif chemokine ligand 11 [KO:K16597]
6369  CCL24; C-C motif chemokine ligand 24 [KO:K21097]
10344  CCL26; C-C motif chemokine ligand 26 [KO:K21096]
56477  CCL28; C-C motif chemokine ligand 28 [KO:K05513]
6361  CCL17; C-C motif chemokine ligand 17 [KO:K21083]
6367  CCL22; C-C motif chemokine ligand 22 [KO:K21095]
6351  CCL4; C-C motif chemokine ligand 4 [KO:K12964]
9560  CCL4L2; C-C motif chemokine ligand 4 like 2 [KO:K12964]
388372  CCL4L1; C-C motif chemokine ligand 4 like 1 [KO:K12964]
6364  CCL20; C-C motif chemokine ligand 20 [KO:K14625]
6346  CCL1; C-C motif chemokine ligand 1 [KO:K05514]
6370  CCL25; C-C motif chemokine ligand 25 [KO:K13072]
6362  CCL18; C-C motif chemokine ligand 18 [KO:K21094]
6363  CCL19; C-C motif chemokine ligand 19 [KO:K05512]
6366  CCL21; C-C motif chemokine ligand 21 [KO:K16062]
2919  CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505]
2920  CXCL2; C-X-C motif chemokine ligand 2 [KO:K05505]
2921  CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505]
6374  CXCL5; C-X-C motif chemokine ligand 5 [KO:K05506]
6372  CXCL6; C-X-C motif chemokine ligand 6 [KO:K05506]
3576  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
5473  PPBP; pro-platelet basic protein [KO:K10029]
5196  PF4; platelet factor 4 [KO:K05407]
5197  PF4V1; platelet factor 4 variant 1 [KO:K05407]
4283  CXCL9; C-X-C motif chemokine ligand 9 [KO:K05416]
3627  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
6373  CXCL11; C-X-C motif chemokine ligand 11 [KO:K12672]
10563  CXCL13; C-X-C motif chemokine ligand 13 [KO:K10032]
6387  CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]
9547  CXCL14; C-X-C motif chemokine ligand 14 [KO:K10033]
6375  XCL1; X-C motif chemokine ligand 1 [KO:K05507]
6846  XCL2; X-C motif chemokine ligand 2 [KO:K22675]
6376  CX3CL1; C-X3-C motif chemokine ligand 1 [KO:K05508]
3586  IL10; interleukin 10 [KO:K05443]
3569  IL6; interleukin 6 [KO:K05405]
3558  IL2; interleukin 2 [KO:K05429]
3606  IL18; interleukin 18 [KO:K05482]
27178  IL37; interleukin 37 [KO:K05485]
29949  IL19; interleukin 19 [KO:K05444]
50604  IL20; interleukin 20 [KO:K22667]
11009  IL24; interleukin 24 [KO:K22668]
7124  TNF; tumor necrosis factor [KO:K03156]
4049  LTA; lymphotoxin alpha [KO:K05468]
8740  TNFSF14; TNF superfamily member 14 [KO:K05477]
8743  TNFSF10; TNF superfamily member 10 [KO:K04721]
146433  IL34; interleukin 34 [KO:K22633]
1435  CSF1; colony stimulating factor 1 [KO:K05453]
1230  CCR1; C-C motif chemokine receptor 1 [KO:K04176]
729230  CCR2; C-C motif chemokine receptor 2 [KO:K04177]
1232  CCR3; C-C motif chemokine receptor 3 [KO:K04178]
1233  CCR4; C-C motif chemokine receptor 4 [KO:K04179]
1234  CCR5; C-C motif chemokine receptor 5 [KO:K04180]
1235  CCR6; C-C motif chemokine receptor 6 [KO:K04181]
1237  CCR8; C-C motif chemokine receptor 8 [KO:K04183]
10803  CCR9; C-C motif chemokine receptor 9 [KO:K04184]
51554  ACKR4; atypical chemokine receptor 4 [KO:K04186]
2826  CCR10; C-C motif chemokine receptor 10 [KO:K04185]
1236  CCR7; C-C motif chemokine receptor 7 [KO:K04182]
3577  CXCR1; C-X-C motif chemokine receptor 1 [KO:K04175]
3579  CXCR2; C-X-C motif chemokine receptor 2 [KO:K05050]
2833  CXCR3; C-X-C motif chemokine receptor 3 [KO:K04188]
643  CXCR5; C-X-C motif chemokine receptor 5 [KO:K04190]
7852  CXCR4; C-X-C motif chemokine receptor 4 [KO:K04189]
57007  ACKR3; atypical chemokine receptor 3 [KO:K04304]
2829  XCR1; X-C motif chemokine receptor 1 [KO:K04193]
1524  CX3CR1; C-X3-C motif chemokine receptor 1 [KO:K04192]
3587  IL10RA; interleukin 10 receptor subunit alpha [KO:K05134]
3588  IL10RB; interleukin 10 receptor subunit beta [KO:K05135]
3570  IL6R; interleukin 6 receptor [KO:K05055]
3572  IL6ST; interleukin 6 cytokine family signal transducer [KO:K05060]
3559  IL2RA; interleukin 2 receptor subunit alpha [KO:K05068]
3560  IL2RB; interleukin 2 receptor subunit beta [KO:K05069]
3561  IL2RG; interleukin 2 receptor subunit gamma [KO:K05070]
8809  IL18R1; interleukin 18 receptor 1 [KO:K05173]
8807  IL18RAP; interleukin 18 receptor accessory protein [KO:K05174]
53832  IL20RA; interleukin 20 receptor subunit alpha [KO:K05136]
53833  IL20RB; interleukin 20 receptor subunit beta [KO:K05137]
58985  IL22RA1; interleukin 22 receptor subunit alpha 1 [KO:K05138]
7132  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
7133  TNFRSF1B; TNF receptor superfamily member 1B [KO:K05141]
4055  LTBR; lymphotoxin beta receptor [KO:K03159]
8764  TNFRSF14; TNF receptor superfamily member 14 [KO:K05152]
8797  TNFRSF10A; TNF receptor superfamily member 10a [KO:K04722]
8795  TNFRSF10B; TNF receptor superfamily member 10b [KO:K04722]
8794  TNFRSF10C; TNF receptor superfamily member 10c [KO:K22701]
8793  TNFRSF10D; TNF receptor superfamily member 10d [KO:K22702]
1436  CSF1R; colony stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
Reference
PMID:12511874
  Authors
Alcami A
  Title
Viral mimicry of cytokines, chemokines and their receptors.
  Journal
Nat Rev Immunol 3:36-50 (2003)
DOI:10.1038/nri980
Reference
PMID:28848041
  Authors
Pontejo SM, Murphy PM
  Title
Chemokines encoded by herpesviruses.
  Journal
J Leukoc Biol 102:1199-1217 (2017)
DOI:10.1189/jlb.4RU0417-145RR
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: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:9325239
  Authors
Smith CA, Smith TD, Smolak PJ, Friend D, Hagen H, Gerhart M, Park L, Pickup DJ, Torrance D, Mohler K, Schooley K, Goodwin RG
  Title
Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors.
  Journal
Virology 236:316-27 (1997)
DOI:10.1006/viro.1997.8730
Reference
PMID:9621074
  Authors
Isegawa Y, Ping Z, Nakano K, Sugimoto N, Yamanishi K
  Title
Human herpesvirus 6 open reading frame U12 encodes a functional beta-chemokine receptor.
  Journal
J Virol 72:6104-12 (1998)
DOI:10.1128/JVI.72.7.6104-6112.1998
Reference
PMID:9600978
  Authors
Damon I, Murphy PM, Moss B
  Title
Broad spectrum chemokine antagonistic activity of a human poxvirus chemokine homolog.
  Journal
Proc Natl Acad Sci U S A 95:6403-7 (1998)
DOI:10.1073/pnas.95.11.6403
Reference
PMID:16365449
  Authors
Dewin DR, Catusse J, Gompels UA
  Title
Identification and characterization of U83A viral chemokine, a broad and potent beta-chemokine agonist for human CCRs with unique selectivity and inhibition by spliced isoform.
  Journal
J Immunol 176:544-56 (2006)
DOI:10.4049/jimmunol.176.1.544
Reference
PMID:16332987
  Authors
Fitzsimons CP, Gompels UA, Verzijl D, Vischer HF, Mattick C, Leurs R, Smit MJ
  Title
Chemokine-directed trafficking of receptor stimulus to different g proteins: selective inducible and constitutive signaling by human herpesvirus 6-encoded chemokine receptor U51.
  Journal
Mol Pharmacol 69:888-98 (2006)
DOI:10.1124/mol.105.015222
Reference
PMID:15536129
  Authors
Wang D, Bresnahan W, Shenk T
  Title
Human cytomegalovirus encodes a highly specific RANTES decoy receptor.
  Journal
Proc Natl Acad Sci U S A 101:16642-7 (2004)
DOI:10.1073/pnas.0407233101
Reference
PMID:22319442
  Authors
Viejo-Borbolla A, Martinez-Martin N, Nel HJ, Rueda P, Martin R, Blanco S, Arenzana-Seisdedos F, Thelen M, Fallon PG, Alcami A
  Title
Enhancement of chemokine function as an immunomodulatory strategy employed by human herpesviruses.
  Journal
PLoS Pathog 8:e1002497 (2012)
DOI:10.1371/journal.ppat.1002497
Reference
PMID:16581912
  Authors
Alejo A, Ruiz-Arguello MB, Ho Y, Smith VP, Saraiva M, Alcami A
  Title
A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.
  Journal
Proc Natl Acad Sci U S A 103:5995-6000 (2006)
DOI:10.1073/pnas.0510462103
Reference
PMID:15890946
  Authors
Tadagaki K, Nakano K, Yamanishi K
  Title
Human herpesvirus 7 open reading frames U12 and U51 encode functional beta-chemokine receptors.
  Journal
J Virol 79:7068-76 (2005)
DOI:10.1128/JVI.79.11.7068-7076.2005
Reference
PMID:12960231
  Authors
Lee C, Liu QH, Tomkowicz B, Yi Y, Freedman BD, Collman RG
  Title
Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways.
  Journal
J Leukoc Biol 74:676-82 (2003)
DOI:10.1189/jlb.0503206
Reference
PMID:14645913
  Authors
Najarro P, Lee HJ, Fox J, Pease J, Smith GL
  Title
Yaba-like disease virus protein 7L is a cell-surface receptor for chemokine CCL1.
  Journal
J Gen Virol 84:3325-36 (2003)
DOI:10.1099/vir.0.19591-0
Reference
PMID:16528029
  Authors
Najarro P, Gubser C, Hollinshead M, Fox J, Pease J, Smith GL
  Title
Yaba-like disease virus chemokine receptor 7L, a CCR8 orthologue.
  Journal
J Gen Virol 87:809-16 (2006)
DOI:10.1099/vir.0.81427-0
Reference
PMID:18286574
  Authors
Catusse J, Spinks J, Mattick C, Dyer A, Laing K, Fitzsimons C, Smit MJ, Gompels UA
  Title
Immunomodulation by herpesvirus U51A chemokine receptor via CCL5 and FOG-2 down-regulation plus XCR1 and CCR7 mimicry in human leukocytes.
  Journal
Eur J Immunol 38:763-77 (2008)
DOI:10.1002/eji.200737618
Reference
PMID:8992974
  Authors
Liu Y, de Waal Malefyt R, Briere F, Parham C, Bridon JM, Banchereau J, Moore KW, Xu J
  Title
The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10 receptor.
  Journal
J Immunol 158:604-13 (1997)
Reference
PMID:15837194
  Authors
Yoon SI, Jones BC, Logsdon NJ, Walter MR
  Title
Same structure, different function crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain.
  Journal
Structure 13:551-64 (2005)
DOI:10.1016/j.str.2005.01.016
Reference
PMID:10677520
  Authors
Kotenko SV, Saccani S, Izotova LS, Mirochnitchenko OV, Pestka S
  Title
Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10).
  Journal
Proc Natl Acad Sci U S A 97:1695-700 (2000)
DOI:10.1073/pnas.97.4.1695
Reference
PMID:15280480
  Authors
Chang WL, Baumgarth N, Yu D, Barry PA
  Title
Human cytomegalovirus-encoded interleukin-10 homolog inhibits maturation of dendritic cells and alters their functionality.
  Journal
J Virol 78:8720-31 (2004)
DOI:10.1128/JVI.78.16.8720-8731.2004
Reference
PMID:11238858
  Authors
Li H, Wang H, Nicholas J
  Title
Detection of direct binding of human herpesvirus 8-encoded interleukin-6 (vIL-6) to both gp130 and IL-6 receptor (IL-6R) and identification of amino acid residues of vIL-6 important for IL-6R-dependent and -independent signaling.
  Journal
J Virol 75:3325-34 (2001)
DOI:10.1128/JVI.75.7.3325-3334.2001
Reference
PMID:11468184
  Authors
Nicot C, Mulloy JC, Ferrari MG, Johnson JM, Fu K, Fukumoto R, Trovato R, Fullen J, Leonard WJ, Franchini G
  Title
HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells.
  Journal
Blood 98:823-9 (2001)
DOI:10.1182/blood.v98.3.823
Reference
PMID:10500212
  Authors
Xiang Y, Moss B
  Title
IL-18 binding and inhibition of interferon gamma induction by human poxvirus-encoded proteins.
  Journal
Proc Natl Acad Sci U S A 96:11537-42 (1999)
DOI:10.1073/pnas.96.20.11537
Reference
PMID:15166422
  Authors
Bartlett NW, Dumoutier L, Renauld JC, Kotenko SV, McVey CE, Lee HJ, Smith GL
  Title
A new member of the interleukin 10-related cytokine family encoded by a poxvirus.
  Journal
J Gen Virol 85:1401-12 (2004)
DOI:10.1099/vir.0.79980-0
Reference
PMID:9557689
  Authors
Strockbine LD, Cohen JI, Farrah T, Lyman SD, Wagener F, DuBose RF, Armitage RJ, Spriggs MK
  Title
The Epstein-Barr virus BARF1 gene encodes a novel, soluble colony-stimulating factor-1 receptor.
  Journal
J Virol 72:4015-21 (1998)
DOI:10.1128/JVI.72.5.4015-4021.1998
Reference
PMID:17229074
  Authors
Snow AL, Martinez OM
  Title
Epstein-Barr virus: evasive maneuvers in the development of PTLD.
  Journal
Am J Transplant 7:271-7 (2007)
DOI:10.1111/j.1600-6143.2006.01650.x
Reference
PMID:22826234
  Authors
Shim AH, Chang RA, Chen X, Longnecker R, He X
  Title
Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein-Barr virus BARF1.
  Journal
Proc Natl Acad Sci U S A 109:12962-7 (2012)
DOI:10.1073/pnas.1205309109
Reference
PMID:11934887
  Authors
Filippova M, Song H, Connolly JL, Dermody TS, Duerksen-Hughes PJ
  Title
The human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNF-induced apoptosis.
  Journal
J Biol Chem 277:21730-9 (2002)
DOI:10.1074/jbc.M200113200
Reference
PMID:12676996
  Authors
Brunetti CR, Paulose-Murphy M, Singh R, Qin J, Barrett JW, Tardivel A, Schneider P, Essani K, McFadden G
  Title
A secreted high-affinity inhibitor of human TNF from Tanapox virus.
  Journal
Proc Natl Acad Sci U S A 100:4831-6 (2003)
DOI:10.1073/pnas.0737244100
Reference
PMID:18723002
  Authors
Sciortino MT, Medici MA, Marino-Merlo F, Zaccaria D, Giuffre-Cuculletto M, Venuti A, Grelli S, Bramanti P, Mastino A
  Title
Involvement of gD/HVEM interaction in NF-kB-dependent inhibition of apoptosis by HSV-1 gD.
  Journal
Biochem Pharmacol 76:1522-32 (2008)
DOI:10.1016/j.bcp.2008.07.030
Reference
PMID:23498957
  Authors
Smith W, Tomasec P, Aicheler R, Loewendorf A, Nemcovicova I, Wang EC, Stanton RJ, Macauley M, Norris P, Willen L, Ruckova E, Nomoto A, Schneider P, Hahn G, Zajonc DM, Ware CF, Wilkinson GW, Benedict CA
  Title
Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses.
  Journal
Cell Host Microbe 13:324-35 (2013)
DOI:10.1016/j.chom.2013.02.003
KO pathway
ko04061   
LinkDB

DBGET integrated database retrieval system