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PMID: 17395582 The virus-specific RNA species, dsRNA or 5'-triphosphate ssRNA, specifically binds to RIG-I through its RNA binding domain. PMID: 17395582, 17190814 RNA binding requires intact helicase and C-terminal autorepression domains. PMID: 17395582 Table2

PMID: 17395582 The virus-specific RNA species, dsRNA or 5'-triphosphate ssRNA, specifically binds to RIG-I through its RNA binding domain. PMID: 17395582, 17190814 RNA binding requires intact helicase and C-terminal autorepression domains.

PMID: 17395582, 15208624, 15708988 RIG-I exhibits strong double-stranded RNA (dsRNA) binding activity in vitro. RIG-I selectively binds with poly(rI:rC), poly(rA:rU), and 5'- and 3'-untranslated regions of hepatitis C virus genomic RNA (which are predicted to form a secondary structure) but not with dsDNA, poly(rA), or yeast tRNA.

PMID: 17395582, 15208624, 15708988 RIG-I exhibits strong double-stranded RNA (dsRNA) binding activity in vitro. RIG-I selectively binds with poly(rI:rC), poly(rA:rU), and 5'- and 3'-untranslated regions of hepatitis C virus genomic RNA (which are predicted to form a secondary structure) but not with dsDNA, poly(rA), or yeast tRNA.

PMID: 17395582, 16127453, 16125763, 16153868 This association and ATP binding to the helicase domain change RIG-I conformation to release CARD for relaying signaling to the downstream molecule (another CARD-containing molecule, IPS-1 (alternatively termed MAVS, VISA, and Cardif)). PMID: 17395582 Table2

PMID: 17395582, 16127453, 16125763, 16153868 This association and ATP binding to the helicase domain change RIG-I conformation to release CARD for relaying signaling to the downstream molecule (another CARD-containing molecule, IPS-1 (alternatively termed MAVS, VISA, and Cardif)). PMID: 17395582 Lys-270 is supposed to be a critical motif for ATP binding within the helicase domain, and in the case of other DExH/D helicases, this motif is crucial for its helicase (unwinding dsRNA) activity.

PMID: 17395582, 16785313, 16713980 MDA5 and RIG-I, which sense a distinct set of viruses (below), commonly transmit signals to IPS-1; thus IPS-1–/– fibroblasts are unresponsive to either set of viruses. PMID: 17395582 Table2

PMID: 17395582, 16785313, 16713980 MDA5 and RIG-I, which sense a distinct set of viruses (below), commonly transmit signals to IPS-1; thus IPS-1–/– fibroblasts are unresponsive to either set of viruses.

PMID: 17395582, 16858409, 15210743, 15210742 The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.

PMID: 17395582, 16858409, 15210743, 15210742 The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.

PMID: 17395582, 16858409, 15210743, 15210742 The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.

PMID: 17395582, 16858409, 15210743, 15210742 The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.

Indirect

PMID: 17395582, 16858409, 15210743, 15210742 The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.

Indirect

PMID: 17395582, 16858409, 15210743, 15210742 The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.

Indirect

PMID: 17395582, 16858409, 15210743, 15210742 The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.

Indirect

PMID: 17395582, 16858409, 15210743, 15210742 The latter involves TNF (tumor necrosis factor) receptor-associating factor 3 (TRAF3) (17) and the protein kinase, I{kappa}B kinase-i (IKK-i ({epsilon})) or TANK-binding kinase-1 (TBK-1) (18, 19), which is responsible for the activation of IRF-3 and -7.

Indirect

PMID: 17395582 The signal is branched at IPS-1, resulting in the activation of NF-kappaB and IRF-3 and -7.

Indirect

PMID: 17395582 The signal is branched at IPS-1, resulting in the activation of NF-kappaB and IRF-3 and -7.

Indirect

PMID: 17395582 The signal is branched at IPS-1, resulting in the activation of NF-kappaB and IRF-3 and -7.

Indirect

PMID: 17395582, 16116171, 16210631, 17020950 LGP2 lacks CARD, suggesting that this helicase is incapable of transmitting a positive signal. Overexpression of LGP2 in cell culture results in the dominant inhibition of virus-induced activation of IFN genes, suggesting its role as a negative regulator; however, its role in vivo is not established. PMID: 17395582 Analyses of RIG-I–/– fibroblasts and conventional dendritic cells (cDCs) showed that RIG-I is essential in Newcastle disease virus (NDV)-induced IFN production.

Indirect

PMID: 17395582, 16116171, 16210631, 17020950 LGP2 lacks CARD, suggesting that this helicase is incapable of transmitting a positive signal. Overexpression of LGP2 in cell culture results in the dominant inhibition of virus-induced activation of IFN genes, suggesting its role as a negative regulator; however, its role in vivo is not established. PMID: 17395582 Analyses of RIG-I–/– fibroblasts and conventional dendritic cells (cDCs) showed that RIG-I is essential in Newcastle disease virus (NDV)-induced IFN production.

Indirect

PMID: 17395582, 15585605, 16932750 pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.

Indirect

PMID: 17395582, 15585605, 16932750 pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.

PMID: 17395582, 15585605, 16932750 pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.

Indirect

PMID: 17395582, 15585605, 16932750 pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.

Indirect

PMID: 17395582, 15585605, 16932750 pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.

Indirect

PMID: 17395582, 15585605, 16932750 pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.

Indirect

PMID: 17395582, 15585605, 16932750 pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.

Indirect

PMID: 17395582, 15585605, 16932750 pDCs adopt a distinct signaling cascade to produce high levels of IFN-alpha and sense viral infection by TLR7/8 and TLR9, activating signaling cascades MyD88, IRAK1/4, TRAF3/6, IKK-alpha, and IRF-7.

PMID: 17395582, 15585605 It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).

PMID: 17395582, 15585605 It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).

Indirect

PMID: 17395582, 15585605 It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).

PMID: 17395582, 15585605 It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).

Indirect

PMID: 17395582, 15585605 It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).

Indirect

PMID: 17395582, 15585605 It has been known that dsRNA activates TLR3 in endosome and signals through TIR domain-containing adaptor inducing IFN-beta (TRIF)/TIR-containing adaptor molecule-1 (TICAM1) resulting in the activation of kinases (TBK-1 or IKK-i) and transcription factors (IRF-3 and -7 and NF-kappaB).

PMID: 17395582 When poly(rI:rC) is injected into mice intravenously, IFN-beta is strictly produced in a MDA5-dependent manner (below), but the TLR-TRIF pathway is dispensable.

Indirect

PMID: 17395582 When poly(rI:rC) is injected into mice intravenously, IFN-beta is strictly produced in a MDA5-dependent manner (below), but the TLR-TRIF pathway is dispensable.

Indirect

PMID: 17395582, 16625202 However, production of IL-8 and IL-12 p40 requires TRIF in addition to MDA5; IL-12 p40 is particularly largely TRIF-dependent.

Indirect

PMID: 17395582, 16625202 However, production of IL-8 and IL-12 p40 requires TRIF in addition to MDA5; IL-12 p40 is particularly largely TRIF-dependent.

Indirect

PMID: 17395582, 16125763, 16585524, 16731946 NS3/4A of hepatitis C virus inactivates IPS-1 by its protease activity.

PMID: 17395582, 16625202 However, production of IL-8 and IL-12 p40 requires TRIF in addition to MDA5; IL-12 p40 is particularly largely TRIF-dependent.