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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.
- 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
- ABCG2 – ATP-binding cassette, sub-family G (WHITE), member
2: HERV-W expression decreased by ABCG2 silencing in trophoblast
cells Evseenko
et al, 2007
- ACTB actin, beta: has a HERV-W long terminal region in its regulatory
region Hegyi,
2013
- ATM ataxia telangiectasia mutated: has a HERV-W long terminal
region in its regulatory region Hegyi,
2013
- 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
- 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
- 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
- CASP9 – caspase 9, apoptosis-related cysteine peptidase:
reduced expression in syncytin-1 transfected apoptotically challenged
HEK293-52 cells Knerr
et al, 2008
- 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
- CD8B – CD8b molecule: See above Bhat
et al, 2011
- CD9 – CD9 molecule: Overexpression of CD9 increases expression
levels of ERVWE1(Syncytin ) Muroi
et al, 2009
- 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.
- 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.
- CD86 – CD86 molecule: See Rolland
et al, 2006.
- CD209 – CD209 molecule (DC-SIGN): The HERV-W env protein
bids to DC-sign Cheynet
et al, 2005
- CDC25A cell division cycle 25A: has a HERV-W long terminal region
in its regulatory region Hegyi,
2013
- 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
- CDKN2B – cyclin-dependent kinase inhibitor 2B (p15, inhibits
CDK4): See Huang
et al, 2013
- CEBPZ – CCAAT/enhancer binding protein (C/EBP), zeta : binds
to the CCAAT motif of the retroviral syncytin gene Cheng
et al, 2004
- 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
- CREB3L1 – cAMP responsive element binding protein 3-like
1 (oasis): Expression induced by syncytin-1 in cultured astrocytes
Antony
et al, 2007
- CREBBP – CREB binding protein: syncytin promoter activity
activated by CREBBP and GCM1 Chuang
et al, 2006
- 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
- 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
- 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
- CYCS – cytochrome c, somatic: Syncytin exertes antiapoptotic
effects via modulation of mitochondrial cytc release Knerr
et al, 2008
- DISC1 disrupted in schizophrenia 1: HERV-W env regulates calcium
influx via TRPC3 channel and depresses DISC1 in human neuroblastoma
cells Chen
et al, 2018.
- 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
- DLD dihydrolipoamide dehydrogenase: has a HERV-W long terminal
region in its regulatory region Hegyi,
2013
- 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.
- 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.
- 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
- 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
- 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
- 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
- ESR2 – estrogen receptor 2 (ER beta) : See Strick
et al, 2007
- FAAH fatty acid amide hydrolase: has a HERV-W long terminal region
in its regulatory region Hegyi,
2013
- 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
- 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
- GABBR1 – gamma-aminobutyric acid (GABA) B receptor, 1: has
a HERV-W long terminal region in its regulatory region Hegyi,
2013
- GATA2 – GATA binding protein 2: Overexpression of SP1, GATA2
and GATA3 induce syncytin promoter activity Cheng
and Handwerger, 2005
- GATA3 – GATA binding protein 3: Overexpression of SP1, GATA2
and GATA3 induce syncytin promoter activity Cheng
and Handwerger, 2005
- GCM1 – glial cells missing homolog 1 (Drosophila) : activates
the syncytin promoter Lin
et al, 2005
- GJA1 – gap junction protein, alpha 1, 43kDa (cx43): HERV-W
env mRNA expression decreased by GJA1 antisense in human cytotrophoblasts
Frendo
et al, 2003
- GSK3B phosphorylation of GSK3ß is required for HERV-W env-mediated
BDNF signaling in human U251 cells.Qin
et al, 2016
- 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
- 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
- HDAC4 – histone deacetylase 4: See Chuang
et al, 2006
- HDAC5 histone deacetylase 5: suppresses syncytin-1 expression
and cell-cell fusion in BeWo cells Chang
et al, 2013
- 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.
- 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
- HLA-G – major histocompatibility complex, class I, G: Syncytin-1
expression increased in HLA-G expressing BeWo cells Wang
et al, 2013
- 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
- HTRA4 – HtrA serine peptidase 4: interacts with syncytin
1: Wang
et al, 2012
- HYAL2 hyaluronoglucosaminidase 2: Binds to ERVW-1Danilkovitch-Miagkova
et al, 2003
- Hypoxia, deferoxamine, and cobalt chloride decrease syncytin messenger
RNA in BeWo cells (placenta choriocarcinoma cells ) Knerr
et al, 2003
- IFNB1 – interferon, beta 1, fibroblast: IFN-beta mediates
down-regulation of HERV-H/F and HERV-W in multiple sclerosis patients
Christensen,
2010.
- 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
- IL1B Expression increased by syncitin overexpression in human
foetal astrocytes and monocyte-derived macrophages Antony
et al, 2004
- 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
- IL10 – interleukin 10: HERV-W env expression in post-mortem
human brains is correlated with IL10 expression Bhat
et al, 2011
- 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
- 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
- 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
- LGALS1 – lectin, galactoside-binding, soluble, 1: upregulates
syncytin protein and mRNA expression in BeWo choriocarcinoma cells
Fischer
et al, 2010
- Lipopolysaccharide: syncytin-1 inhibits LPS-stimulated cytokine
responses in human blood cells Tolosa
et al, 2012
- LNX1 ligand of numb-protein X 1, E3 ubiquitin protein ligase :
Binds to ERVW-1 Guo
et al, 2012
- 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.
- MAP2 microtubule-associated protein 2: has a HERV-W long terminal
region in its regulatory region Hegyi,
2013
- MAP4 microtubule-associated protein 4: has a HERV-W long terminal
region in its regulatory region Hegyi,
2013
- MAPK10 mitogen-activated protein kinase 10: has a HERV-W long
terminal region in its regulatory region Hegyi,
2013
- 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
- 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
- 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
- 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
- NR1H3 – nuclear receptor subfamily 1, group H, member 3
: See Ave
et al, 2011
- NR3C2 nuclear receptor subfamily 3, group C, member 2 (mineralocorticoid
receptor;): has a HERV-W long terminal region in its regulatory
region Hegyi,
2013
- NRCAM neuronal cell adhesion molecule: has a HERV-W long terminal
region in its regulatory region Hegyi,
2013
- 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
- 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
- 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
- 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
- POLR2A – polymerase (RNA) II (DNA directed) polypeptide
A, 220kDa : Herv-w is transcribed by RNA polymerase II: Lavie
et al, 2004
- POMC proopiomelanocortin: ACTH and CRH upregulate HERV-W retroviral
genes in the pituitary Buslei
et al, 2014
- POU2F1 – POU class 2 homeobox 1 (oct-1): Transcription silencer
for the HERV-W Long terminal repeat Lee
et al, 2003
- PPARG – peroxisome proliferator-activated receptor gamma:
regulates retroviral Syncytin-1 expression Ruebner
et al, 2012
- 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.
- Progesterone upregulates HERV-W env (syncytin-1) expression in
human trophoblasts Noorali
et al, 2009
- RAPGEF3 – Rap guanine nucleotide exchange factor (GEF) 3
(epac1)Stimulation activates syncytin-1 expession : Chang
et al, 2011
- 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
- RXRA – retinoid X receptor, alpha: regulates retroviral
Syncytin-1 expression Ruebner
et al, 2012
- SHISA5 shisa homolog 5 (Xenopus laevis): has a HERV-W long terminal
region in its regulatory region Hegyi,
2013
- SLC1A4 – solute carrier family 1 (glutamate/neutral amino
acid transporter), member 4 : HERV-W envelope glycoprotein Receptor
Lavillette
et al, 2002
- SLC1A5 – solute carrier family 1 (neutral amino acid transporter),
member 5: HERV-W envelope glycoprotein Receptor Lavillette
et al, 2002
- SLC18A1 solute carrier family 18 (vesicular monoamine), member
1: has a HERV-W long terminal region in its regulatory region Hegyi,
2013
- SP1 – Sp1 transcription factor: Overexpression of SP1, GATA2
and GATA3 induce syncytin promoter activity Cheng
and Handwerger, 2005
- STARD7 – StAR-related lipid transfer (START) domain containing
7|:Syncytin-1 expression increased by STARD7 knockdown in JEG-3
cells
- STMN1 – stathmin 1: cAMP-enhanced syncytin expression and
cell fusion in BeWo cells inhibited by stathmin knockdown Yoshie
et al, 2008.
- STOX1 – storkhead box 1: Syncytin expression modified by
STOX1 knockout in choriocarcinoma cells Rigour
et al, 2008.
- TCF4 – transcription factor 4 : TCF4 signalling directly
targets the GCM1/syncytin pathway Matsuura
et al, 2011
- 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
- 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
- TGFB3 – transforming growth factor, beta 3: See Strick
et al, 2007
- TLR4 – toll-like receptor 4: activated by HERV-W Perron
et al, 2009
- TNF induced by syncytin-1 in astrocytes Antony
et al, 2007
- TRPC3 transient receptor potential cation channel subfamily C
member 3 : HERV-W env regulates calcium influx via TRPC3 channel
and depresses DISC1 in human neuroblastoma cells Chen
et al, 2018.
- Valproic acid upregulates HERV-W element expresion in glioblastoma
cell lines Diem
et al, 2012
- XBP1 , Increased expression of XBP1, BiP, and NOS2 in human fetal
astrocytes transfected with Syncytin-1 Deslauriers
et al, 2011
- 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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