_enti_e7
_enti_e8
_enti_e9
_enti_e1
_enti_e2
_enti_e3
_enti_e4
_enti_e55
_enti_e15
_enti_e152
_enti_e149
_enti_e151
_enti_e59
_enti_e53
_enti_e16
_enti_e17
_enti_e150
_enti_e153
_enti_e148
_enti_e154
_enti_e51
_enti_e52
_enti_e54
_enti_e50
_enti_e56
_enti_e156
_enti_e57
_enti_e61
_enti_e58
_enti_e155
_enti_e62
_enti_e60
g3_fact_g3
g1_fact_g4
g2_fact_g5
g1_fact_g1
g1_fact_g14
g2_fact_g12
g2_fact_g13
g1_fact_g2
p1_propro_p1
PMID: 17667934,12697090
Following the discovery of TLR4, TLR2 was found to be the
receptor for components of the Gram-positive bacterial cell wall,
recognizing triacyl lipopeptides in combination with TLR1, and diacyl lipopeptides in combination with TLR6.
c1 cso30:c:InputProcess connector
c2 cso30:c:InputProcess connector
c3 cso30:c:OutputProcess connector
p1_propro_p2
PMID: 17667934,12697090
Following the discovery of TLR4, TLR2 was found to be the
receptor for components of the Gram-positive bacterial cell wall,
recognizing triacyl lipopeptides in combination with TLR1, and diacyl lipopeptides in combination with TLR6.
c4 cso30:c:InputProcess connector
c5 cso30:c:InputProcess connector
c6 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 17667934,11607032
TLR3 recognises doublestranded
RNA
c7 cso30:c:InputProcess connector
c9 cso30:c:InputProcess connector
c8 cso30:c:OutputProcess connector
p4_propro_p4
PMID: 17667934,17283206,11323673,11489966
TLR5 recognises bacterial flagellin
c10 cso30:c:InputProcess connector
c11 cso30:c:InputProcess connector
c12 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 17667934,14976262,11812998,11130078
TLR7/8
recognise single-stranded viral RNA, and TLR-9 recognises unmethylated
CpG DNA motifs present in both viruses and bacteria
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p5_propro_p6
PMID: 17667934,14976262,11812998,11130078
TLR7/8
recognise single-stranded viral RNA, and TLR-9 recognises unmethylated
CpG DNA motifs present in both viruses and bacteria
c16 cso30:c:InputProcess connector
c17 cso30:c:InputProcess connector
c18 cso30:c:OutputProcess connector
p5_propro_p7
PMID: 17667934,14976262,11812998,11130078
TLR7/8
recognise single-stranded viral RNA, and TLR-9 recognises unmethylated
CpG DNA motifs present in both viruses and bacteria
c19 cso30:c:InputProcess connector
c20 cso30:c:InputProcess connector
c21 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 17667934,11057907
TLR3 signals via the MyD88-independent pathway using the alternate
adaptor protein TRIF
c22 cso30:c:InputProcess connector
c23 cso30:c:InputProcess connector
c24 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 17667934,16497588
TRIF interacts with
tumour necrosis factor (TNF) receptor associated factor 3 (TRAF3)
3 to activate TRAF-family-member-associated NFkB activator
(TANK)-binding kinase 1 (TBK1), and the non-canonical inhibitor
of NFkB (IkappaB) kinase , IKKi
c25 cso30:c:InputProcess connector
c26 cso30:c:InputProcess connector
c27 cso30:c:OutputProcess connector
c42 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 17667934,16497588
TRIF interacts with
tumour necrosis factor (TNF) receptor associated factor 3 (TRAF3)
3 to activate TRAF-family-member-associated NFkB activator
(TANK)-binding kinase 1 (TBK1), and the non-canonical inhibitor
of NFkB (IkB) kinase , IKKi
c28 cso30:c:InputAssociation connector
c29 cso30:c:InputProcess connector
c30 cso30:c:OutputProcess connector
p11_propro_p11
PMID: 17667934
These kinases directly phosphorylate
interferon regulatory factor-3 (IRF-3).
PMID: 17667934,17190786
TBK1/IKKi phosphorylate IRF-3 and IRF-7,
inducing a type-1 IFN response.
PMID: 17667934,15841462
Otsuka et al showed that NS3 binds TBK1 to act as a
competitive inhibitor of the TBK1-IRF-3 interaction, to reduce IRF-3
activation and therefore downstream IFNb induction
c31 cso30:c:InputAssociation connector
c32 cso30:c:InputProcess connector
c251 cso30:c:InputInhibitor connector
c33 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 17667934
Phosphorylated IRF-3 forms a
dimer before translocating to the nucleus, where it induces expression
of IFNb.
c34 cso30:c:InputProcess connector
c35 cso30:c:OutputProcess connector
p13_propro_p13
c36 cso30:c:InputProcess connector
c37 cso30:c:OutputProcess connector
p14_propro_p14
c38 cso30:c:InputAssociation connector
c39 cso30:c:OutputProcess connector
p15_propro_p15
PMID: 17667934,15665823
TRIF is also able to interact with receptor-interacting protein
1 and TRAF6 to induce a late phase proinflammatory cytokine
response
c40 cso30:c:InputProcess connector
c41 cso30:c:InputProcess connector
c276 cso30:c:OutputProcess connector
p15_propro_p16
PMID: 17667934,15665823
TRIF is also able to interact with receptor-interacting protein
1 and TRAF6 to induce a late phase proinflammatory cytokine
response
c43 cso30:c:InputProcess connector
c44 cso30:c:InputProcess connector
c45 cso30:c:OutputProcess connector
p17_propro_p17
c46 cso30:c:InputProcess connector
c47 cso30:c:InputProcess connector
c48 cso30:c:OutputProcess connector
p18_propro_p18
PMID: 17667934,16497588
TLR4 uses the
adaptor TRAM to recruit TRIF and induce a type-1 IFN response via
the MyD88-independent pathway described above
PMID: 17667934
Figure2
c49 cso30:c:InputProcess connector
c50 cso30:c:InputProcess connector
c51 cso30:c:OutputProcess connector
p18_propro_p19
PMID: 17667934,16497588
TLR4 uses the
adaptor TRAM to recruit TRIF and induce a type-1 IFN response via
the MyD88-independent pathway described above
PMID: 17667934
Figure2
c52 cso30:c:InputProcess connector
c53 cso30:c:InputProcess connector
c54 cso30:c:OutputProcess connector
p20_propro_p20
PMID: 17667934,12447441
In
contrast, TLR4 uses the coadaptor Mal to recruit MyD88 to its TIR
domain
c55 cso30:c:InputProcess connector
c56 cso30:c:InputProcess connector
c57 cso30:c:OutputProcess connector
p20_propro_p21
PMID: 17667934,12447441
In
contrast, TLR4 uses the coadaptor Mal to recruit MyD88 to its TIR
domain
c58 cso30:c:InputProcess connector
c59 cso30:c:InputProcess connector
c60 cso30:c:OutputProcess connector
p22_propro_p22
PMID: 17667934,17457343,15928677
Stimulation of the MyD88-dependent pathway initiates a
downstream signalling cascade involving sequential activation of
primary and secondary kinases including the interleukin-1 receptor
(IL-1R) associated kinases -4 and -1 (IRAK-4, and -1), TRAF6 and
TGF-b-activated kinase (TAK1).
PMID: 17667934
Figure2
c61 cso30:c:InputAssociation connector
c62 cso30:c:InputProcess connector
c63 cso30:c:OutputProcess connector
p22_propro_p23
PMID: 17667934,17457343,15928677
Stimulation of the MyD88-dependent pathway initiates a
downstream signalling cascade involving sequential activation of
primary and secondary kinases including the interleukin-1 receptor
(IL-1R) associated kinases -4 and -1 (IRAK-4, and -1), TRAF6 and
TGF-b-activated kinase (TAK1).
PMID: 17667934
Figure2
c64 cso30:c:InputAssociation connector
c65 cso30:c:InputProcess connector
c66 cso30:c:OutputProcess connector
p22_propro_p24
PMID: 17667934,17457343,15928677
Stimulation of the MyD88-dependent pathway initiates a
downstream signalling cascade involving sequential activation of
primary and secondary kinases including the interleukin-1 receptor
(IL-1R) associated kinases -4 and -1 (IRAK-4, and -1), TRAF6 and
TGF-b-activated kinase (TAK1).
PMID: 17667934
Figure2
c67 cso30:c:InputAssociation connector
c68 cso30:c:InputProcess connector
c69 cso30:c:OutputProcess connector
p22_propro_p25
PMID: 17667934,17457343,15928677
Stimulation of the MyD88-dependent pathway initiates a
downstream signalling cascade involving sequential activation of
primary and secondary kinases including the interleukin-1 receptor
(IL-1R) associated kinases -4 and -1 (IRAK-4, and -1), TRAF6 and
TGF-b-activated kinase (TAK1).
PMID: 17667934
Figure2
c70 cso30:c:InputAssociation connector
c71 cso30:c:InputProcess connector
c72 cso30:c:OutputProcess connector
p26_propro_p26
PMID: 17667934,15208624
Activated TAK1, in a complex with the TAK-1
binding proteins, TAB1 and TAB2, phosphorylates the IKK complex
and the MAP kinases (JNK, ERK and p38), leading to activation of
transcription factors nuclear factor-kappa B (NF-KappaB), and/or activating
protein-1 (AP-1), respectively.
c73 cso30:c:InputAssociation connector
c74 cso30:c:InputProcess connector
c75 cso30:c:OutputProcess connector
p26_propro_p27
PMID: 17667934,15208624
Activated TAK1, in a complex with the TAK-1
binding proteins, TAB1 and TAB2, phosphorylates the IKK complex
and the MAP kinases (JNK, ERK and p38), leading to activation of
transcription factors nuclear factor-kappa B (NF-KappaB), and/or activating
protein-1 (AP-1), respectively.
c76 cso30:c:InputAssociation connector
c77 cso30:c:InputProcess connector
c78 cso30:c:OutputProcess connector
p26_propro_p28
PMID: 17667934,15208624
Activated TAK1, in a complex with the TAK-1
binding proteins, TAB1 and TAB2, phosphorylates the IKK complex
and the MAP kinases (JNK, ERK and p38), leading to activation of
transcription factors nuclear factor-kappa B (NF-KappaB), and/or activating
protein-1 (AP-1), respectively.
c79 cso30:c:InputAssociation connector
c80 cso30:c:InputProcess connector
c81 cso30:c:OutputProcess connector
p26_propro_p29
PMID: 17667934,15208624
Activated TAK1, in a complex with the TAK-1
binding proteins, TAB1 and TAB2, phosphorylates the IKK complex
and the MAP kinases (JNK, ERK and p38), leading to activation of
transcription factors nuclear factor-kappa B (NF-KappaB), and/or activating
protein-1 (AP-1), respectively.
c82 cso30:c:InputProcess connector
c84 cso30:c:InputAssociation connector
c83 cso30:c:OutputProcess connector
p30_propro_p30
PMID: 17667934,15208624
Activated TAK1, in a complex with the TAK-1
binding proteins, TAB1 and TAB2, phosphorylates the IKK complex
and the MAP kinases (JNK, ERK and p38), leading to activation of
transcription factors nuclear factor-kappa B (NF-KappaB), and/or activating
protein-1 (AP-1), respectively.
PMID: 17667934,12566418
A52R inhibits NF-kB induction by multiple
TLRs via interaction with IRAK2 and TRAF6
c85 cso30:c:InputProcess connector
c87 cso30:c:InputAssociation connector
c227 cso30:c:InputInhibitor connector
c86 cso30:c:OutputProcess connector
p30_propro_p31
PMID: 17667934,15208624
Activated TAK1, in a complex with the TAK-1
binding proteins, TAB1 and TAB2, phosphorylates the IKK complex
and the MAP kinases (JNK, ERK and p38), leading to activation of
transcription factors nuclear factor-kappa B (NF-KappaB), and/or activating
protein-1 (AP-1), respectively.
c88 cso30:c:InputAssociation connector
c89 cso30:c:InputProcess connector
c90 cso30:c:OutputProcess connector
p30_propro_p32
PMID: 17667934,15208624
Activated TAK1, in a complex with the TAK-1
binding proteins, TAB1 and TAB2, phosphorylates the IKK complex
and the MAP kinases (JNK, ERK and p38), leading to activation of
transcription factors nuclear factor-kappa B (NF-KappaB), and/or activating
protein-1 (AP-1), respectively.
c91 cso30:c:InputAssociation connector
c92 cso30:c:InputProcess connector
c93 cso30:c:OutputProcess connector
p30_propro_p33
PMID: 17667934,15208624
Activated TAK1, in a complex with the TAK-1
binding proteins, TAB1 and TAB2, phosphorylates the IKK complex
and the MAP kinases (JNK, ERK and p38), leading to activation of
transcription factors nuclear factor-kappa B (NF-KappaB), and/or activating
protein-1 (AP-1), respectively.
c94 cso30:c:InputAssociation connector
c95 cso30:c:InputProcess connector
c96 cso30:c:OutputProcess connector
p34_propro_p34
PMID: 17667934,16497588
In contrast, TLR7/8 and TLR9 are able to use MyD88 to induce
expression of both proinflammatory cytokines and type-1 IFN
c97 cso30:c:InputProcess connector
c98 cso30:c:InputProcess connector
c99 cso30:c:OutputProcess connector
p35_propro_p35
PMID: 17667934,16306936,16306937,16604075,15800576,15361868,16612387,16125763
Following nucleic acid recognition,MyD88 forms a signalling complex
with IRAK-1, IRAK-4, TRAF6, TRAF3, IKKa and a precursor of
osteopontin (OPN)
c100 cso30:c:InputProcess connector
c101 cso30:c:InputProcess connector
c102 cso30:c:OutputProcess connector
p36_propro_p36
PMID: 17667934
The MyD88- IRAK-4-
TRAF6 complex activates NF-KappaB and AP-1 as described above.
c103 cso30:c:InputAssociation connector
c104 cso30:c:InputProcess connector
c105 cso30:c:OutputProcess connector
p36_propro_p37
PMID: 17667934
The MyD88- IRAK-4-
TRAF6 complex activates NF-KappaB and AP-1 as described above.
c106 cso30:c:InputAssociation connector
c107 cso30:c:InputProcess connector
c108 cso30:c:OutputProcess connector
p38_propro_p38
PMID: 17667934
In
addition, the recruitment of IRAK-1, TRAF-3, IKKa and OPN allows
TLR7/8 and TLR9 to activate IRF-7, which translocates to the nucleus
to regulate the expression of type-1 IFN genes, especially IFNa
c109 cso30:c:InputAssociation connector
c110 cso30:c:InputProcess connector
c111 cso30:c:OutputProcess connector
p39_propro_p39
PMID: 17667934
In
addition, the recruitment of IRAK-1, TRAF-3, IKKa and OPN allows
TLR7/8 and TLR9 to activate IRF-7, which translocates to the nucleus
to regulate the expression of type-1 IFN genes, especially IFNa
c112 cso30:c:InputProcess connector
c113 cso30:c:OutputProcess connector
p40_propro_p40
PMID: 17667934
In
addition, the recruitment of IRAK-1, TRAF-3, IKKa and OPN allows
TLR7/8 and TLR9 to activate IRF-7, which translocates to the nucleus
to regulate the expression of type-1 IFN genes, especially IFNa
c114 cso30:c:InputAssociation connector
c115 cso30:c:OutputProcess connector
p41_propro_p41
PMID: 17667934,15208624
It
was recognized that TLR-independent mechanisms existed to detect
intracellular viral infection, and in 2004 Yoneyama and colleagues identified RIG-I as a cytosolic sensor of dsRNA produced during
viral replication, triggering a type-1 interferon and proinflammatory cytokine response
c116 cso30:c:InputProcess connector
c117 cso30:c:InputProcess connector
c118 cso30:c:OutputProcess connector
p42_propro_p42
PMID: 17667934
MDA-5 was identified soon after as a second
CARD-containing helicase
PMID: 17667934
Figure 2
c120 cso30:c:InputProcess connector
c226 cso30:c:InputProcess connector
c121 cso30:c:OutputProcess connector
p43_propro_p43
PMID: 17667934
Following dsRNA binding, RIG-I undergoes a conformational shift
allowing self-association and CARD interaction with a downstream
adaptor protein, IFN-b promoter stimulator (IPS-1).
c122 cso30:c:InputProcess connector
c123 cso30:c:InputProcess connector
c124 cso30:c:OutputProcess connector
p43_propro_p44
PMID: 17667934
Following dsRNA binding, RIG-I undergoes a conformational shift
allowing self-association and CARD interaction with a downstream
adaptor protein, IFN-b promoter stimulator (IPS-1).
c125 cso30:c:InputProcess connector
c126 cso30:c:InputProcess connector
c127 cso30:c:OutputProcess connector
p45_propro_p45
PMID: 17667934,16127453
Like RIG-I,
MDA5 associates with IPS-1 via a CARDCARD interaction following
dsRNA binding
c128 cso30:c:InputProcess connector
c129 cso30:c:InputProcess connector
c130 cso30:c:OutputProcess connector
p46_propro_p46
PMID: 17667934,16858409
IPS-1 interacts with TRAF3 via its non-CARD region to activate
TBK-1 and IKKi
c131 cso30:c:InputProcess connector
c132 cso30:c:InputProcess connector
c133 cso30:c:OutputProcess connector
p46_propro_p47
PMID: 17667934,16858409
IPS-1 interacts with TRAF3 via its non-CARD region to activate
TBK-1 and IKKi
c134 cso30:c:InputProcess connector
c135 cso30:c:InputProcess connector
c136 cso30:c:OutputProcess connector
p48_propro_p48
PMID: 17667934,16858409
IPS-1 interacts with TRAF3 via its non-CARD region to activate
TBK-1 and IKKi
c138 cso30:c:InputProcess connector
c137 cso30:c:InputAssociation connector
c139 cso30:c:OutputProcess connector
p49_propro_p49
PMID: 17667934,16858409
IPS-1 interacts with TRAF3 via its non-CARD region to activate
TBK-1 and IKKi
c140 cso30:c:InputAssociation connector
c141 cso30:c:InputProcess connector
c142 cso30:c:OutputProcess connector
p50_propro_p50
PMID: 17667934,17190786
TBK1/IKKi phosphorylate IRF-3 and IRF-7,
inducing a type-1 IFN response.
c143 cso30:c:InputAssociation connector
c144 cso30:c:InputProcess connector
c145 cso30:c:OutputProcess connector
p51_propro_p51
PMID: 17667934,17190786
TBK1/IKKi phosphorylate IRF-3 and IRF-7,
inducing a type-1 IFN response.
c146 cso30:c:InputAssociation connector
c147 cso30:c:OutputProcess connector
p51_propro_p52
PMID: 17667934,17190786
TBK1/IKKi phosphorylate IRF-3 and IRF-7,
inducing a type-1 IFN response.
c148 cso30:c:InputAssociation connector
c149 cso30:c:OutputProcess connector
p53_propro_p53
PMID: 17667934,16127453
IPS-1
interacts with FADD, an adaptor involved in death receptor signalling
via its death domain
c150 cso30:c:InputProcess connector
c151 cso30:c:InputProcess connector
c152 cso30:c:OutputProcess connector
p53_propro_p54
PMID: 17667934,16127453
IPS-1
interacts with FADD, an adaptor involved in death receptor signalling
via its death domain
c153 cso30:c:InputProcess connector
c154 cso30:c:InputProcess connector
c155 cso30:c:OutputProcess connector
p55_propro_p55
PMID: 17667934,17190786
FADD forms a complex with caspase-10, and
caspase-8; the caspase cleavage products produced are specifically
involved in downstream NF-kB activation and proinflammatory
cytokine production
c156 cso30:c:InputProcess connector
c157 cso30:c:InputProcess connector
c158 cso30:c:InputProcess connector
c159 cso30:c:OutputProcess connector
p55_propro_p56
PMID: 17667934,17190786
FADD forms a complex with caspase-10, and
caspase-8; the caspase cleavage products produced are specifically
involved in downstream NF-kB activation and proinflammatory
cytokine production
c160 cso30:c:InputProcess connector
c161 cso30:c:InputProcess connector
c162 cso30:c:InputProcess connector
c163 cso30:c:OutputProcess connector
p57_propro_p57
PMID: 17667934,11607032
Poly(I:C), a synthetic
dsRNA analogue, was first demonstrated to be a ligand for TLR3 by
Alexopoulou and colleagues in 2001, inducing type-1 interferons
and proinflammatory cytokines in a MyD88-independent manner
c164 cso30:c:InputProcess connector
c165 cso30:c:InputProcess connector
c166 cso30:c:OutputProcess connector
p58_propro_p58
PMID: 17667934,11812998,12032557
TLR7 and 8 also recognize synthetic antiviral compounds,
including imidazoquinolines (imiquimod and R848) and certain
guanine nucleotide analogues (loxoribine).
c167 cso30:c:InputProcess connector
c168 cso30:c:InputProcess connector
c169 cso30:c:OutputProcess connector
p58_propro_p59
PMID: 17667934,11812998,12032557
TLR7 and 8 also recognize synthetic antiviral compounds,
including imidazoquinolines (imiquimod and R848) and certain
guanine nucleotide analogues (loxoribine).
c170 cso30:c:InputProcess connector
c171 cso30:c:InputProcess connector
c172 cso30:c:OutputProcess connector
p58_propro_p60
PMID: 17667934,11812998,12032557
TLR7 and 8 also recognize synthetic antiviral compounds,
including imidazoquinolines (imiquimod and R848) and certain
guanine nucleotide analogues (loxoribine).
c173 cso30:c:InputProcess connector
c174 cso30:c:InputProcess connector
c175 cso30:c:OutputProcess connector
p58_propro_p61
PMID: 17667934,11812998,12032557
TLR7 and 8 also recognize synthetic antiviral compounds,
including imidazoquinolines (imiquimod and R848) and certain
guanine nucleotide analogues (loxoribine).
c176 cso30:c:InputProcess connector
c177 cso30:c:InputProcess connector
c178 cso30:c:OutputProcess connector
p58_propro_p62
PMID: 17667934,11812998,12032557
TLR7 and 8 also recognize synthetic antiviral compounds,
including imidazoquinolines (imiquimod and R848) and certain
guanine nucleotide analogues (loxoribine).
c179 cso30:c:InputProcess connector
c180 cso30:c:InputProcess connector
c181 cso30:c:OutputProcess connector
p58_propro_p63
PMID: 17667934,11812998,12032557
TLR7 and 8 also recognize synthetic antiviral compounds,
including imidazoquinolines (imiquimod and R848) and certain
guanine nucleotide analogues (loxoribine).
c182 cso30:c:InputProcess connector
c183 cso30:c:InputProcess connector
c184 cso30:c:OutputProcess connector
p64_propro_p64
PMID: 17667934
The F protein of RSV activates TLR4
c185 cso30:c:InputProcess connector
c186 cso30:c:InputProcess connector
c187 cso30:c:OutputProcess connector
p65_propro_p65
PMID: 17667934,17082626,14739339,12163593,15521019,12663765,16973959,17082589
TLR2 has been shown to be activated by a number of viruses or
viral proteins, including the haemaglutinin protein (HA) of measles
virus (MV), HSV-1, the core and NS3 proteins of hepatitis C virus
(HCV), the envelope glycoproteins B and H of human CMV and vaccinia virus (VV).
c188 cso30:c:InputProcess connector
c189 cso30:c:InputProcess connector
c190 cso30:c:OutputProcess connector
p65_propro_p66
PMID: 17667934,17082626,14739339,12163593,15521019,12663765,16973959,17082589
TLR2 has been shown to be activated by a number of viruses or
viral proteins, including the haemaglutinin protein (HA) of measles
virus (MV), HSV-1, the core and NS3 proteins of hepatitis C virus
(HCV), the envelope glycoproteins B and H of human CMV and vaccinia virus (VV).
c191 cso30:c:InputProcess connector
c192 cso30:c:InputProcess connector
c193 cso30:c:OutputProcess connector
p65_propro_p67
PMID: 17667934,17082626,14739339,12163593,15521019,12663765,16973959,17082589
TLR2 has been shown to be activated by a number of viruses or
viral proteins, including the haemaglutinin protein (HA) of measles
virus (MV), HSV-1, the core and NS3 proteins of hepatitis C virus
(HCV), the envelope glycoproteins B and H of human CMV and vaccinia virus (VV).
c194 cso30:c:InputProcess connector
c195 cso30:c:InputProcess connector
c196 cso30:c:OutputProcess connector
p65_propro_p68
PMID: 17667934,17082626,14739339,12163593,15521019,12663765,16973959,17082589
TLR2 has been shown to be activated by a number of viruses or
viral proteins, including the haemaglutinin protein (HA) of measles
virus (MV), HSV-1, the core and NS3 proteins of hepatitis C virus
(HCV), the envelope glycoproteins B and H of human CMV and vaccinia virus (VV).
c197 cso30:c:InputProcess connector
c198 cso30:c:InputProcess connector
c199 cso30:c:OutputProcess connector
p65_propro_p69
PMID: 17667934,17082626,14739339,12163593,15521019,12663765,16973959,17082589
TLR2 has been shown to be activated by a number of viruses or
viral proteins, including the haemaglutinin protein (HA) of measles
virus (MV), HSV-1, the core and NS3 proteins of hepatitis C virus
(HCV), the envelope glycoproteins B and H of human CMV and vaccinia virus (VV).
c200 cso30:c:InputProcess connector
c201 cso30:c:InputProcess connector
c202 cso30:c:OutputProcess connector
p65_propro_p70
PMID: 17667934,17082626,14739339,12163593,15521019,12663765,16973959,17082589
TLR2 has been shown to be activated by a number of viruses or
viral proteins, including the haemaglutinin protein (HA) of measles
virus (MV), HSV-1, the core and NS3 proteins of hepatitis C virus
(HCV), the envelope glycoproteins B and H of human CMV and vaccinia virus (VV).
c203 cso30:c:InputProcess connector
c204 cso30:c:InputProcess connector
c205 cso30:c:OutputProcess connector
p72_propro_p72
PMID: 17667934
When patient PBMCs were stimulated with the specific TLR2
ligand Pam-3-Cys, relative suppression of TNFa induction was noted
in the HBeAg-positive group, confirming functional significance.
c207 cso30:c:InputProcess connector
c208 cso30:c:InputProcess connector
c209 cso30:c:OutputProcess connector
p73_propro_p73
PMID: 17667934
When patient PBMCs were stimulated with the specific TLR2
ligand Pam-3-Cys, relative suppression of TNFa induction was noted
in the HBeAg-positive group, confirming functional significance.
c211 cso30:c:InputInhibitor connector
c210 cso30:c:OutputProcess connector
p71_propro_p71
PMID: 17667934,17190786
FADD forms a complex with caspase-10, and
caspase-8; the caspase cleavage products produced are specifically
involved in downstream NF-kB activation and proinflammatory
cytokine production
PMID: 17667934,17049367,15563593
The V proteins of paramyxoviruses have been shown to interact with
MDA5, but not RIG-I, to inhibit dsRNA-induced activation of IRF3
and NF-kB
c206 cso30:c:InputAssociation connector
c212 cso30:c:InputProcess connector
c264 cso30:c:InputInhibitor connector
c213 cso30:c:OutputProcess connector
p74_propro_p74
PMID: 17667934,17190786
FADD forms a complex with caspase-10, and
caspase-8; the caspase cleavage products produced are specifically
involved in downstream NF-kB activation and proinflammatory
cytokine production
c214 cso30:c:InputAssociation connector
c215 cso30:c:InputProcess connector
c216 cso30:c:OutputProcess connector
p71_propro_p75
PMID: 17667934,17190786
FADD forms a complex with caspase-10, and
caspase-8; the caspase cleavage products produced are specifically
involved in downstream NF-kB activation and proinflammatory
cytokine production
c217 cso30:c:InputAssociation connector
c218 cso30:c:InputProcess connector
c219 cso30:c:OutputProcess connector
p76_propro_p76
PMID: 17667934,12163593
The proinflammatory response to
the HA protein of measles leads to the upregulation of CD150, an
entry receptor for MV, and therefore the HA-TLR2 interaction may
contribute to MV spread and pathogenesis
c221 cso30:c:InputAssociation connector
c220 cso30:c:OutputProcess connector
p77_propro_p77
PMID: 17667934,12566418
A52R inhibits NF-kB induction by multiple
TLRs via interaction with IRAK2 and TRAF6
c222 cso30:c:InputProcess connector
c223 cso30:c:InputProcess connector
c224 cso30:c:InputProcess connector
c225 cso30:c:OutputProcess connector
p78_propro_p78
PMID: 17667934,15998638
Interestingly, the A52R-TRAF6 interaction has been shown to simultaneously activate
the MAP kinase p38 to enhance TLR-induced IL-10 induction the
immunoregulatory role of IL-10 supports that this may be another
virulence mechanism.
c228 cso30:c:InputProcess connector
c229 cso30:c:InputProcess connector
c230 cso30:c:OutputProcess connector
p79_propro_p79
c231 cso30:c:InputAssociation connector
c232 cso30:c:InputProcess connector
c233 cso30:c:OutputProcess connector
p80_propro_p80
PMID: 17667934,15998638
Interestingly, the A52R-TRAF6 interaction has been shown to simultaneously activate
the MAP kinase p38 to enhance TLR-induced IL-10 induction the
immunoregulatory role of IL-10 supports that this may be another
virulence mechanism.
c234 cso30:c:InputAssociation connector
c236 cso30:c:InputAssociation connector
c237 cso30:c:InputAssociation connector
c235 cso30:c:OutputProcess connector
p81_propro_p81
PMID: 17667934,15710891
NS3/4a was
found to inhibit the dsRNA-TLR3 response by cleaving the adaptor
TRIF between amino acids (aa) 372 and 373.
c238 cso30:c:InputAssociation connector
c239 cso30:c:InputProcess connector
c247 cso30:c:InputInhibitor connector
c240 cso30:c:OutputProcess connector
c241 cso30:c:OutputProcess connector
p82_propro_p82
PMID: 17667934,16177806,15710891,15710892
NS3/4a also interfered
with the cytoplasmic response to dsRNA, by cleaving IPS-1 at aa Cys-
508, the downstream adaptor of RIG-I.
PMID: 17667934,16585524
The effect was able to be blocked using a specific pharmacological
inhibitor of the NS3/4a protease
c242 cso30:c:InputAssociation connector
c243 cso30:c:InputProcess connector
c246 cso30:c:InputInhibitor connector
c244 cso30:c:OutputProcess connector
c245 cso30:c:OutputProcess connector
p83_propro_p83
PMID: 17667934,15841462
Otsuka et al showed that NS3 binds TBK1 to act as a
competitive inhibitor of the TBK1-IRF-3 interaction, to reduce IRF-3
activation and therefore downstream IFNb induction
c248 cso30:c:InputProcess connector
c249 cso30:c:InputProcess connector
c250 cso30:c:OutputProcess connector
p84_propro_p84
PMID: 17667934
GBV-B encodes a
similar NS3/4a protease, which has also been shown to disrupt RIG-I
signalling by targeting IPS-1 for cleavage
c252 cso30:c:InputAssociation connector
c253 cso30:c:InputProcess connector
c254 cso30:c:OutputProcess connector
c255 cso30:c:OutputProcess connector
p85_propro_p85
PMID: 17667934,17438296
Yang et al found that the 3ABC precursor of the 3C(pro) cysteine protease of
HAV was targeted to the mitochondrial membrane where it cleaved
IPS-1, disrupting signalling activity
c256 cso30:c:InputProcess connector
c257 cso30:c:OutputProcess connector
p86_propro_p86
PMID: 17667934,17438296
Yang et al found that the 3ABC precursor of the 3C(pro) cysteine protease of
HAV was targeted to the mitochondrial membrane where it cleaved
IPS-1, disrupting signalling activity
c259 cso30:c:InputProcess connector
c258 cso30:c:InputAssociation connector
c260 cso30:c:OutputProcess connector
p87_propro_p87
PMID: 17667934,17049367,15563593
The V proteins of paramyxoviruses have been shown to interact with
MDA5, but not RIG-I, to inhibit dsRNA-induced activation of IRF3
and NF-kB
c261 cso30:c:InputProcess connector
c262 cso30:c:InputProcess connector
c119 cso30:c:InputProcess connector
c263 cso30:c:OutputProcess connector
p88_propro_p88
PMID: 17667934,17049367,15563593
The V proteins of paramyxoviruses have been shown to interact with
MDA5, but not RIG-I, to inhibit dsRNA-induced activation of IRF3
and NF-kB
c265 cso30:c:InputAssociation connector
c266 cso30:c:InputProcess connector
c268 cso30:c:InputInhibitor connector
c267 cso30:c:OutputProcess connector
p89_propro_p89
PMID: 17667934,17079289
More recently it has been shown that NS1 also directly interacts with RIG-I to inhibit downstream activation
of IRF-3.
c269 cso30:c:InputProcess connector
c270 cso30:c:InputProcess connector
c271 cso30:c:OutputProcess connector
p90_propro_p90
PMID: 17667934,17079289
More recently it has been shown that NS1 also directly interacts with RIG-I to inhibit downstream activation
of IRF-3.
c274 cso30:c:InputProcess connector
c272 cso30:c:InputAssociation connector
c275 cso30:c:InputInhibitor connector
c273 cso30:c:OutputProcess connector
p91_propro_p91
PMID: 17667934
Figure2
c277 cso30:c:InputAssociation connector
c278 cso30:c:InputProcess connector
c279 cso30:c:OutputProcess connector
p91_propro_p92
PMID: 17667934
Figure2
c280 cso30:c:InputAssociation connector
c281 cso30:c:InputProcess connector
c282 cso30:c:OutputProcess connector
p93_propro_p93
PMID: 17667934
Figure2
c283 cso30:c:InputProcess connector
c284 cso30:c:InputProcess connector
c285 cso30:c:OutputProcess connector
TLR2:TLR1_enti_e5
TLR2:TLR1
Triacyl lipopeptides_enti_e6
Triacyl lipopeptides
TLR2:TLR1:Triacyl Lipopeptides_enti_e11
TLR2:TLR1:Triacyl Lipopeptides
diacyl lipopeptides_enti_e12
diacyl lipopeptides
TLR2:TLR6_enti_e13
TLR2:TLR6
TLR2:TLR6:diacyl lipopeptides_enti_e14
TLR2:TLR6:diacyl lipopeptides
TLR3_enti_MO000019398
TLR3
dsRNA:TLR3_enti_MO000041446
dsRNA:TLR3
dsRNA_enti_MO000022224
dsRNA
TLR5_enti_MO000019399
TLR5
flagellin_enti_MO000022185
flagellin
TLR5:flagellin_enti_e18
TLR5:flagellin
TLR7_enti_MO000042126
TLR7
TLR8_enti_MO000042007
TLR8
ssRNA_enti_e19
ssRNA
TLR7:ssRNA_enti_e20
TLR7:ssRNA
TLR8:ssRNA_enti_e21
TLR8:ssRNA
TLR9_enti_MO000042012
TLR9
CpG DNA_enti_e22
CpG DNA
TLR9:CpG DNA_enti_e23
TLR9:CpG DNA
TRIF_enti_MO000041125
TRIF
dsRNA:TLR3:TRIF_enti_e24
dsRNA:TLR3:TRIF
TRAF3_enti_MO000016963
TRAF3
dsRNA:TLR3:TRIF:TRAF3_enti_e25
dsRNA:TLR3:TRIF:TRAF3
TBK-1:Ikk-i_enti_e26
TBK-1:Ikk-i
TBK-1:Ikk-i{active}_enti_e27
TBK-1:Ikk-i{active}
IRF-3_enti_MO000007694
IRF-3
IRF-3{p}_enti_MO000041456
IRF-3{p}
IRF-3{p}:IRF-3{p}_enti_e28
IRF-3{p}:IRF-3{p}
IRF-3{p}:IRF-3{p}_enti_e29
IRF-3{p}:IRF-3{p}
IFN-beta_enti_G010228
IFN-beta
RIP1_enti_MO000000065
RIP1
dsRNA:TLR3:TRIF:RIP1_enti_e30
dsRNA:TLR3:TRIF:RIP1
TRAF6_enti_e31
TRAF6
dsRNA:TLR3:TRIF:TRAF6_enti_e32
dsRNA:TLR3:TRIF:TRAF6
LPS_enti_e33
LPS
TLR4_enti_e34
TLR4
LPS:TLR4_enti_e35
LPS:TLR4
TRAM_enti_e36
TRAM
LPS:TLR4:TRAM_enti_e37
LPS:TLR4:TRAM
LPS:TLR4:TRAM:TRIF_enti_e38
LPS:TLR4:TRAM:TRIF
Mal_enti_e39
Mal
LPS:TLR4:Mal_enti_e40
LPS:TLR4:Mal
MyD88_enti_e41
MyD88
LPS:TLR4:Mal:MyD88_enti_e42
LPS:TLR4:Mal:MyD88
IRAK4_enti_e43
IRAK4
IRAK4{active}_enti_e44
IRAK4{active}
IRAK1_enti_e45
IRAK1
IRAK1{active}_enti_e46
IRAK1{active}
TRAF6{active}_enti_e47
TRAF6{active}
TAK1:TAB1:TAB2_enti_e48
TAK1:TAB1:TAB2
TAK1{active}:TAB1:TAB2_enti_e49
TAK1{active}:TAB1:TAB2
IKK complex_enti_e63
IKK complex
IKK complex{p}_enti_e64
IKK complex{p}
JNK_enti_e65
JNK
JNK{p}_enti_e66
JNK{p}
ERK_enti_e67
ERK
ERK{p}_enti_e68
ERK{p}
p38_enti_e69
p38
p38{p}_enti_e70
p38{p}
NF-kappaB_enti_e71
NF-kappaB
NF-kappaB{active}_enti_e72
NF-kappaB{active}
AP-1_enti_e73
AP-1
AP-1{active}_enti_e74
AP-1{active}
TLR7:ssRNA:MyD88_enti_e75
TLR7:ssRNA:MyD88
IRAK-1:IRAK-4:TRAF6:TRAF3:IKK-alpha:OPN_enti_e76
IRAK-1:IRAK-4:TRAF6:TRAF3:IKK-alpha:OPN
TLR7:ssRNA:MyD88:IRAK-1:IRAK-4:TRAF6:TRAF3:IKK-alpha:OPN_enti_e77
TLR7:ssRNA:MyD88:IRAK-1:IRAK-4:TRAF6:TRAF3:IKK-alpha:OPN
IRF-7_enti_e78
IRF-7
IRF-7{active}_enti_e79
IRF-7{active}
IRF-7{active}_enti_e80
IRF-7{active}
IFN-alpha_enti_e81
IFN-alpha
dsRNA_enti_e82
dsRNA
RIG-I_enti_e83
RIG-I
RIG-I:dsRNA_enti_e84
RIG-I:dsRNA
MDA5_enti_e85
MDA5
MDA5:dsRNA_enti_e86
MDA5:dsRNA
RIG-I:dsRNA:RIG-I_enti_e10
RIG-I:dsRNA:RIG-I
IPS_enti_e87
IPS
RIG-I:dsRNA:RIG-I:IPS_enti_e88
RIG-I:dsRNA:RIG-I:IPS
MDA5:dsRNA:IPS_enti_e89
MDA5:dsRNA:IPS
TRAF3_enti_e90
TRAF3
RIG-I:dsRNA:RIG-I:IPS:TRAF3_enti_e91
RIG-I:dsRNA:RIG-I:IPS:TRAF3
MDA5:dsRNA:IPS:TRAF3_enti_e92
MDA5:dsRNA:IPS:TRAF3
IRF-7{p}_enti_e93
IRF-7{p}
Type I IFN _enti_e94
Type I IFN
FADD_enti_e95
FADD
RIG-I:dsRNA:RIG-I:TRAF3:FADD_enti_e96
RIG-I:dsRNA:RIG-I:TRAF3:FADD
MDA5:dsRNA:IPS:TRAF3:FADD_enti_e97
MDA5:dsRNA:IPS:TRAF3:FADD
caspase-8_enti_e98
caspase-8
Caspase-10_enti_e99
Caspase-10
MDA5:dsRNA:IPS:TRAF3:FADD:caspase-8:caspase-10_enti_e100
MDA5:dsRNA:IPS:TRAF3:FADD:caspase-8:caspase-10
RIG-I:dsRNA:RIG-I:TRAF3:FADD:caspase-8:caspase-10_enti_e101
RIG-I:dsRNA:RIG-I:TRAF3:FADD:caspase-8:caspase-10
Poly I:C_enti_e102
Poly I:C
TLR3:Poly I:C_enti_e103
TLR3:Poly I:C
Imiquimod_enti_e104
Imiquimod
TLR7:Imiquimod_enti_e105
TLR7:Imiquimod
TLR8:Imiquimod_enti_e106
TLR8:Imiquimod
R848_enti_e107
R848
TLR7:R848_enti_e108
TLR7:R848
TLR8:R848_enti_e109
TLR8:R848
Loxoribine_enti_e110
Loxoribine
TLR8:Loxoribine_enti_e111
TLR8:Loxoribine
TLR7:Loxoribine_enti_e112
TLR7:Loxoribine
F protein_enti_e113
F protein
F protein:TLR4_enti_e114
F protein:TLR4
TLR2_enti_e115
TLR2
HA_enti_e116
HA
TLR2:HA_enti_e117
TLR2:HA
HSV-1_enti_e118
HSV-1
TLR2:HSV1_enti_e119
TLR2:HSV1
core_enti_e120
core
TLR2:core_enti_e121
TLR2:core
NS3_enti_e122
NS3
TLR2:NS3_enti_e123
TLR2:NS3
glycoprotein B_enti_e124
glycoprotein B
TLR2:glycoprotein B_enti_e125
TLR2:glycoprotein B
glycoprotein H_enti_e126
glycoprotein H
TLR2:glycoprotein H_enti_e127
TLR2:glycoprotein H
Pam-3-Cys_enti_e129
Pam-3-Cys
TLR2:Pam-3-Cys_enti_e130
TLR2:Pam-3-Cys
TNF-alpha_enti_e131
TNF-alpha
NS3/4a_enti_e128
NS3/4a
Proinflammtory cytokine_enti_e132
Proinflammtory cytokine
Proinflammtory cytokine_enti_e133
Proinflammtory cytokine
CD150_enti_e134
CD150
IRAk2_enti_e135
IRAk2
A52R_enti_e136
A52R
IRAK2:A52R:TRAF6_enti_e137
IRAK2:A52R:TRAF6
A52R:TRAF6_enti_e138
A52R:TRAF6
p38{active}_enti_e139
p38{active}
IL-10_enti_e140
IL-10
IL-10_enti_e141
IL-10
protein remnants_enti_e142
NS3/4a inhibitor_enti_e143
NS3/4a inhibitor
NS3_enti_e144
NS3
TBK1_enti_e145
TBK1
NS3:TBK1_enti_e146
NS3:TBK1
GBV-B encoded protease_enti_e147
GBV-B encoded protease
3 ABC precursor_enti_e157
3 ABC precursor
3 ABC precursor_enti_e158
3 ABC precursor
protein remnants_enti_e159
V proteins_enti_e160
V proteins
V proteins:MDA5:dsRNA_enti_e161
V proteins:MDA5:dsRNA
IRF-3{active}_enti_e162
IRF-3{active}
NS1_enti_e163
NS1
RIG-I:dsRNA:NS1_enti_e164
RIG-I:dsRNA:NS1
dsRNA:TLR3:TRIF:RIP1_enti_e165
dsRNA:TLR3:TRIF:RIP1
MyD88_enti_e166
MyD88