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ERVWE1 (Syncytin-1) OMIM

Atlas of Genetics and Cytogenetics in Oncology and Haematology ERVW-1

Biogrid ERVW-1

NCBI Retrovirus genomes

Coffin JM, Hughes SH, Varmus HE, editors. Retroviruses. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 1997. NCBI Books

Human endogenous virus database HERVd

Wikipedia

All the virology on the WWW

 

 

Host proteins used by the HERV-W retrovirus during its life cycle (includes effects of and on the captured retroviral gene syncytin-1 )

If you know of other interactions, (or corrections) please with Pubmed ID, gene symbol/accession number and interacting protein. Thank you.

  1. 25-hydroxycholesterol, 7-ketocholesterol, 22(R)-hydroxycholesterol] and the LXR agonist T0901317 at non-toxic doses decreased expression of GCM-1 and HERV-W mRNA in placental trophoblasts Ave et al, 2011
  2. ABCG2 – ATP-binding cassette, sub-family G (WHITE), member 2: HERV-W expression decreased by ABCG2 silencing in trophoblast cells Evseenko et al, 2007
  3. ACTB actin, beta: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  4. ATM ataxia telangiectasia mutated: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  5. BCL9L – B-cell CLL/lymphoma 9-like: the GCM1/syncytin pathway is significantly downregulated in the placenta of BCL9L-deficient mice Matsuura et al, 2011
  6. BDNF Overexpression of HERV-w env in human U251 glioma cells upregulated BDNF, NTRK2 and dopamine receptor D3 and increased the phosphorylation of CREB1 Huang et al, 2011
  7. C5 – complement component 5: The complement membrane attack complex composed of C5, C6, C7, C8 (C8A, C8B and C8G subunits) and C9 (activated by infection or hypoxia (in placentae) binds to villous trophoblast injury in vivo and upregulates syncytin-1 Rampersad et al, 2008
  8. CASP9 – caspase 9, apoptosis-related cysteine peptidase: reduced expression in syncytin-1 transfected apoptotically challenged HEK293-52 cells Knerr et al, 2008
  9. CD3E – CD3e molecule, epsilon (CD3-TCR complex): HERV-W env expression in post-mortem human brains is correlated with the expression of inflammatory genes , granzyme A, CD3e, CD8ß, TGFß, IL12 and IL23 Bhat et al, 2011
  10. CD8B – CD8b molecule: See above Bhat et al, 2011
  11. CD9 – CD9 molecule: Overexpression of CD9 increases expression levels of ERVWE1(Syncytin ) Muroi et al, 2009
  12. CD14 – CD14 molecule: TLR4 and CD14 PRR are involved in the proinflammatory effects of the MSRV protein ENV-SU on human monocytes Rolland et al, 2006.
  13. CD80 – CD80 molecule: The surface expression of both CD80 and CD86 was up-regulated in monocytes following MSRV (HERV-W family) treatment Rolland et al, 2006.
  14. CD86 – CD86 molecule: See Rolland et al, 2006.
  15. CD209 – CD209 molecule (DC-SIGN): The HERV-W env protein bids to DC-sign Cheynet et al, 2005
  16. CDC25A cell division cycle 25A: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  17. CDK1 – cyclin-dependent kinase 1; syncytin-1 knockdown inhibited BeWo cell growth and DNA synthesis inducing upregulation of CDKN2B (p15) and downregulation of CDK4, E2F1, PCNA, and c-Myc, which consequently led to a reduced level of CDK1 Huang et al, 2013
  18. CDKN2B – cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4): See Huang et al, 2013
  19. CEBPZ – CCAAT/enhancer binding protein (C/EBP), zeta : binds to the CCAAT motif of the retroviral syncytin gene Cheng et al, 2004
  20. CREB1 – cAMP responsive element binding protein 1: Overexpression of HERV-w env in human U251 glioma cells upregulated BDNF, NTRK2 and dopamine receptor D3 and increased the phosphorylation of CREB1 Huang et al, 2011
  21. CREB3L1 – cAMP responsive element binding protein 3-like 1 (oasis): Expression induced by syncytin-1 in cultured astrocytes Antony et al, 2007
  22. CREBBP – CREB binding protein: syncytin promoter activity activated by CREBBP and GCM1 Chuang et al, 2006
  23. CRH – corticotropin releasing hormone: stimulates the expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts Fahlbusch et al, 2012.ACTH and CRH upregulate HERV-W retroviral genes in the pituitary Buslei et al, 2014
  24. CTNNB1 – catenin (cadherin-associated protein), beta 1, 88kDa: ß-catenin/BCL9-Like (BCL9L)/T-cell factor 4 (TCF4) signalling directly targets the GCM1/syncytin pathway Matsuura et al, 2011
  25. CXCL10 – chemokine (C-X-C motif) ligand 10 : Syncytin-1 recombinant ectodomain inhibits the production of the Th1 cytokines TNF and IFNG and CXCL10 in human blood cells Tolosa et al, 2012
  26. CYCS – cytochrome c, somatic: Syncytin exertes antiapoptotic effects via modulation of mitochondrial cytc release Knerr et al, 2008
  27. DDIT3 – DNA-damage-inducible transcript 3: Human fetal astrocytes, overexpressing Syncytin-1, demonstrated significantly increased transcript levels of DDIT3, HSPA5 (bip), EIF2AK3 (perk) , PDIA3 ERp57, and CREB3L1 (oasis) Antony et al, 2007
  28. DLD dihydrolipoamide dehydrogenase: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  29. DLX3 – distal-less homeobox 3: Down-regulation of DLX3 in primary villous trophoblast cells and a trophoblast-derived cell line sdecreases expression of differentiation markers, 3ßHSD, ßhCG and syncytin Chui et al, 2012.
  30. DNMT3A – DNA (cytosine-5-)-methyltransferase 3 alpha: DNMT3a and HELLS could be responsible for a decreased Syncytin-1 expression by promoter hypermethylation of ERVW-1 Ruebner et al, 2013.
  31. DRD3 – dopamine receptor D3: Overexpression of HERV-w env in human U251 glioma cells upregulated BDNF, NTRK2 and dopamine receptor D3 and increased the phosphorylation of CREB1 Huang et al, 2011
  32. E2F1 – E2F transcription factor 1: syncytin-1 knockdown inhibited BeWo cell growth and DNA synthesis inducing upregulation of CDKN2B (p15) and downregulation of CDK4, E2F1, PCNA, and c-Myc, which consequently led to a reduced level of CDK1 Huang et al, 2013
  33. EIF2AK3 – eukaryotic translation initiation factor 2-alpha kinase 3 : Human fetal astrocytes, overexpressing Syncytin-1, demonstrated significantly increased transcript levels of DDIT3, HSPA5 (bip), EIF2AK3 (perk) , PDIA2 ERp57, and CREB3L1 (oasis) Antony et al, 2007
  34. ESR1 – estrogen receptor 1: Steroid hormone treatment of primary emdometrial carcinoma cells and cell lines induced Syncytin-1 via a HERV-W estrogen response element Strick et al, 2007
  35. ESR2 – estrogen receptor 2 (ER beta) : See Strick et al, 2007
  36. FAAH fatty acid amide hydrolase: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  37. Ferulic acid ( hydroxycinnamic acid)The decrease in oligodendrocyte numbers and increase in hypertrophied astrocytes caused by syncytin expression were reversed by daily treatment with ferulic acid Antony et al, 2004
  38. FURIN – furin (paired basic amino acid cleaving enzyme) : The herv-w envelope preprotein is processed by protease(s) and posesses a furin cleavage site Cheynet et al, 2005
  39. GABBR1 – gamma-aminobutyric acid (GABA) B receptor, 1: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  40. GATA2 – GATA binding protein 2: Overexpression of SP1, GATA2 and GATA3 induce syncytin promoter activity Cheng and Handwerger, 2005
  41. GATA3 – GATA binding protein 3: Overexpression of SP1, GATA2 and GATA3 induce syncytin promoter activity Cheng and Handwerger, 2005
  42. GCM1 – glial cells missing homolog 1 (Drosophila) : activates the syncytin promoter Lin et al, 2005
  43. GJA1 – gap junction protein, alpha 1, 43kDa (cx43): HERV-W env mRNA expression decreased by GJA1 antisense in human cytotrophoblasts Frendo et al, 2003
  44. GZMA – granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3) : HERV-W env expression in post-mortem human brains is correlated with the expression of inflammatory genes , granzyme A, CD3e, CD8ß, TGFß, IL12 and IL23 Bhat et al, 2011
  45. HDAC3 – histone deacetylase 3: associates with the proximal GCM1-binding site in the syncytin promoter: HDAC3 and 4 repress the syncytin promoter activity activated by CBP and GCM1 Chuang et al, 2006
  46. HDAC4 – histone deacetylase 4: See Chuang et al, 2006
  47. HDAC5 histone deacetylase 5: suppresses syncytin-1 expression and cell-cell fusion in BeWo cells Chang et al, 2013
  48. HELLS – helicase, lymphoid-specific: DNMT3a and HELLS could be responsible for a decreased Syncytin-1 expression by promoter hypermethylation of ERVW-1 Ruebner et al, 2013.
  49. HLA-DRA – major histocompatibility complex, class II, DR alpha: HERV-W env expression in post-mortem human brains is correlated with IL10 expression Bhat et al, 2011
  50. HLA-G – major histocompatibility complex, class I, G: Syncytin-1 expression increased in HLA-G expressing BeWo cells Wang et al, 2013
  51. HSPA5 – heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)(Bip) Increased expression of XBP1, BiP, and NOS2 in human fetal astrocytes transfected with Syncytin-1 Deslauriers et al, 2011
  52. HTRA4 – HtrA serine peptidase 4: interacts with syncytin 1: Wang et al, 2012
  53. HYAL2 hyaluronoglucosaminidase 2: Binds to ERVW-1Danilkovitch-Miagkova et al, 2003
  54. Hypoxia, deferoxamine, and cobalt chloride decrease syncytin messenger RNA in BeWo cells (placenta choriocarcinoma cells ) Knerr et al, 2003
  55. IFNB1 – interferon, beta 1, fibroblast: IFN-beta mediates down-regulation of HERV-H/F and HERV-W in multiple sclerosis patients Christensen, 2010.
  56. IFNG – interferon, gamma: Syncytin-1 recombinant ectodomain inhibits the production of the Th1 cytokines TNF and IFNG and CXCL10 in human blood cells Tolosa et al, 2012
  57. IL1B Expression increased by syncitin overexpression in human foetal astrocytes and monocyte-derived macrophages Antony et al, 2004
  58. IL6 – interleukin 6 (interferon, beta 2) : TNFalpha, interferon-gamma, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while interferon-beta is inhibitory Mameli et al, 2007
  59. IL10 – interleukin 10: HERV-W env expression in post-mortem human brains is correlated with IL10 expression Bhat et al, 2011
  60. IL12A – interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35) : HERV-W env expression in post-mortem human brains is correlated with the expression of inflammatory genes , granzyme A, CD3e, CD8ß, TGFß, IL12 and IL23 Bhat et al, 2011
  61. IL12B – interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) : Expression increased (alog with TNF, IL1B, IL6), by an ENV-SU protein of the MSRV virus (of the HERV-W family) Rolland et al, 2006
  62. IL23A – interleukin 23, alpha subunit p19: HERV-W env expression in post-mortem human brains is correlated with the expression of inflammatory genes , granzyme A, CD3e, CD8ß, TGFß, IL12 and IL23 Bhat et al, 2011
  63. LGALS1 – lectin, galactoside-binding, soluble, 1: upregulates syncytin protein and mRNA expression in BeWo choriocarcinoma cells Fischer et al, 2010
  64. Lipopolysaccharide: syncytin-1 inhibits LPS-stimulated cytokine responses in human blood cells Tolosa et al, 2012
  65. LNX1 ligand of numb-protein X 1, E3 ubiquitin protein ligase : Binds to ERVW-1 Guo et al, 2012
  66. KCNN3 – potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3: overexpression of HERV-W env protein elevated the levels of KCNN3 in human neuroblastoma cells Li et al, 2013.
  67. MAP2 microtubule-associated protein 2: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  68. MAP4 microtubule-associated protein 4: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  69. MAPK10 mitogen-activated protein kinase 10: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  70. MYB v-myb avian myeloblastosis viral oncogene homolog: Syncytin-1 3'-LTR mutatedprotein, observed in urothelial cell carcinoma, binds to MYB Yu et al, 2013
  71. MYC – v-myc myelocytomatosis viral oncogene homolog (avian) : syncytin-1 knockdown inhibited BeWo cell growth and DNA synthesis inducing upregulation of CDKN2B (p15) and downregulation of CDK4, E2F1, PCNA, and c-Myc, which consequently led to a reduced level of CDK1 Huang et al, 2013
  72. NOS2 – nitric oxide synthase 2, inducible: Increased expression of XBP1, BiP, and NOS2 in human fetal astrocytes transfected with Syncytin-1 Deslauriers et al, 2011
  73. NR1H2 – nuclear receptor subfamily 1, group H, member 2 (lxrb): 25-hydroxycholesterol, 7-ketocholesterol, 22(R)-hydroxycholesterol] and the LXR agonist T0901317 at non-toxic doses decreased expression of GCM-1 and HERV-W mRNA in placental trophoblasts Ave et al, 2011
  74. NR1H3 – nuclear receptor subfamily 1, group H, member 3 : See Ave et al, 2011
  75. NR3C2 nuclear receptor subfamily 3, group C, member 2 (mineralocorticoid receptor;): has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  76. NRCAM neuronal cell adhesion molecule: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  77. NTRK2 – neurotrophic tyrosine kinase, receptor, type 2 : Overexpression of HERV-w env in human U251 glioma cells upregulated BDNF, NTRK2 and dopamine receptor D3 and increased the phosphorylation of CREB1 Huang et al, 2011
  78. PARD6A – par-6 partitioning defective 6 homolog alpha (C. elegans): Par6 overexpression in the presence of forskolin decreased syncytin 1 levels in choriocarcinoma BeWo cells Sivasubramaniyam et al, 2013
  79. PCNA – proliferating cell nuclear antigen: syncytin-1 knockdown inhibited BeWo cell growth and DNA synthesis inducing upregulation of CDKN2B (p15) and downregulation of CDK4, E2F1, PCNA, and c-Myc, which consequently led to a reduced level of CDK1 Huang et al, 2013
  80. PDIA3 – protein disulfide isomerase family A, member 3: Human fetal astrocytes, overexpressing Syncytin-1, demonstrated significantly increased transcript levels of DDIT3, HSPA5 (bip), EIF2AK3 (perk) , PDIA3 (ERp57), and CREB3L1 (oasis) Antony et al, 2007
  81. POLR2A – polymerase (RNA) II (DNA directed) polypeptide A, 220kDa : Herv-w is transcribed by RNA polymerase II: Lavie et al, 2004
  82. POMC proopiomelanocortin: ACTH and CRH upregulate HERV-W retroviral genes in the pituitary Buslei et al, 2014
  83. POU2F1 – POU class 2 homeobox 1 (oct-1): Transcription silencer for the HERV-W Long terminal repeat Lee et al, 2003
  84. PPARG – peroxisome proliferator-activated receptor gamma: regulates retroviral Syncytin-1 expression Ruebner et al, 2012
  85. PRKACA – protein kinase, cAMP-dependent, catalytic, alpha: CD9 increases GCM1 expression via the cAMP/PKA signaling pathway, resulting in the increase in ERVWE1 expression Muroi et al, 2009.
  86. Progesterone upregulates HERV-W env (syncytin-1) expression in human trophoblasts Noorali et al, 2009
  87. RAPGEF3 – Rap guanine nucleotide exchange factor (GEF) 3 (epac1)Stimulation activates syncytin-1 expession : Chang et al, 2011
  88. RELA – v-rel reticuloendotheliosis viral oncogene homolog A (avian): TNF, interferon-gamma, IL6, and interleukin-1 activate the ERVWE1 promoter, while interferon-beta is inhibitory: Effects of TNF mediated via the p65 subunit of NF-kappaB (RELA) ,Mameli et al, 2007
  89. RXRA – retinoid X receptor, alpha: regulates retroviral Syncytin-1 expression Ruebner et al, 2012
  90. SHISA5 shisa homolog 5 (Xenopus laevis): has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  91. SLC1A4 – solute carrier family 1 (glutamate/neutral amino acid transporter), member 4 : HERV-W envelope glycoprotein Receptor Lavillette et al, 2002
  92. SLC1A5 – solute carrier family 1 (neutral amino acid transporter), member 5: HERV-W envelope glycoprotein Receptor Lavillette et al, 2002
  93. SLC18A1 solute carrier family 18 (vesicular monoamine), member 1: has a HERV-W long terminal region in its regulatory region Hegyi, 2013
  94. SP1 – Sp1 transcription factor: Overexpression of SP1, GATA2 and GATA3 induce syncytin promoter activity Cheng and Handwerger, 2005
  95. STARD7 – StAR-related lipid transfer (START) domain containing 7|:Syncytin-1 expression increased by STARD7 knockdown in JEG-3 cells
  96. STMN1 – stathmin 1: cAMP-enhanced syncytin expression and cell fusion in BeWo cells inhibited by stathmin knockdown Yoshie et al, 2008.
  97. STOX1 – storkhead box 1: Syncytin expression modified by STOX1 knockout in choriocarcinoma cells Rigour et al, 2008.
  98. TCF4 – transcription factor 4 : TCF4 signalling directly targets the GCM1/syncytin pathway Matsuura et al, 2011
  99. TGFB1 – transforming growth factor, beta 1 TGF-beta (TGFB1 and TGFB3) overrides Syncytin-1-mediated cell-cell fusions. Interactions between Syncytin-1 and TGF-beta may contribute to the etiology of Endometrial carcinomas Strick et al, 2007
    1. HERV-W env expression in post-mortem human brains is correlated with the expression of inflammatory genes , granzyme A, CD3e, CD8ß, TGFß, IL12 and IL23 Bhat et al, 2011
  100. TGFB3 – transforming growth factor, beta 3: See Strick et al, 2007
  101. TLR4 – toll-like receptor 4: activated by HERV-W Perron et al, 2009
  102. TNF induced by syncytin-1 in astrocytes Antony et al, 2007
  103. Valproic acid upregulates HERV-W element expresion in glioblastoma cell lines Diem et al, 2012
  104. XBP1 , Increased expression of XBP1, BiP, and NOS2 in human fetal astrocytes transfected with Syncytin-1 Deslauriers et al, 2011
  105. Caffeine and aspirin increase the expression of HERV-W env and gag in human SH-SY5Y neuroblastoma cells Liu et al, 2013.

Bulk experiments

The Human Endogenous Retrovirus Envelope Glycoprotein, Syncytin-1, Regulates Neuroinflammation and Its Receptor Expression in Multiple Sclerosis: A Role for Endoplasmic Reticulum Chaperones in Astrocytes Antony et al, 2007

Genes increased and decreased in Syncytin-1-expressing astrocytes showing a similar profile in lesions from MS patients: UP: CEBPG RCN1 TNFRSF6 DOWN: ACAT2 AQP11 CCNI CNP GAD2 HSPA6 HTR7 KIF5A MAP1D NEUROD2 PEG3 PVALB RAB5B RPS4Y1 SCD SPOCK2 SST XTL3

Gene profile in Syncytin-1-expressing astrocytes showing up-regulation and down-regulation of immune response, myelin-related, and ER stress genes UP: ADAM10 CMT4B2 FLJ14281 FLJ23560 HSPD1 HSPH1 SERP1 SOCS5 STAT1 STCH TLR4
DOWN: ACAT2 AQP11 CCNI CNP GAD2 HSPA6 HTR7 KIF5A MAP1D NEUROD2 PEG3 PVALB RAB5B RPS4Y1 SCD SPOCK2 SST XTL3

Age- and disease-dependent HERV-W envelope allelic variation in brain: association with neuroimmune gene expression.Bhat et al, 2011

Genes whose expression correlate with that of the HERV-W env protein in human brain samples ARG1 ATF4 CD274 CD34 CD86 FCGR3A HAVCR2 IFNA2 IFNA3 IL1A MAP2 NCAM1 NES NFKB1 STAT3 STAT4 STAT6 TBX21 TGFB1 TLR4 TRIM5 VIM XBP1

  • Influenza A/WSN/33 and Herpes simplex (HSV-1) viruses modulate the expression of HERV-W elements in human cell-lines Nellåker et al, 2006.
  • The Epstein-Barr protein EBVgp350 stimulates the expression of HERV-W/MSRV/syncytin-1 via the NFKB1 pathway Mameli et al, 2012.


Associated diseases

  • Alzheimer's disease: HERV-W levels detected in patients with Alzheimer's dementia only when TNF expression was also evident (2 of 6 cases) Johnston et al, 2001
  • Autism: Higher percentage of HERV-H and HERV-W positive samples in Autism spectrum disorder patients (peripheral blood mononuclear cells) Balestrieri et al, 2012
  • Breast cancer : degree of syncytin expression constituted a positive prognostic indicator for recurrence-free survival Larsson et al, 2007.
  • Motor neuron disease (elevated levels of syncytin in muscle biopsies ) Oluwole et al, 2007
  • Multiple Sclerosis: Many papers reviewed in Dolei and Perron 2009
  • Bipolar disorder and Schizophrenia: Increased expression in peripheral blood mononuclear cells: Perron et al, 2012
  • Depression: Reduced expression of human endogenous retrovirus (HERV)-W GAG protein in the cingulate gyrus and hippocampus in schizophrenia, bipolar disorder, and depression Weis et al, 2007.
 
 
 
     

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Last update: January 28, 2017