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IRF3Interferon Regulatory Factor 3
IRF3IFN Regulatory Factor 3
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Activation of IRF3 and NF-[kappa]B are the principal targets of TRIF-dependent pathway.
However, besides the recognition of DNA by TLR9, a different TLR9-independent mechanism has been proposed allowing the recognition of dsDNA in the cytoplasm of macrophages and in nonimmune cells, but also inducing activation of IRF3, NF-[kappa][beta] , and IFN-[alpha] (30).
It is known as IFN-[alpha] promoter stimulator (IPS-1), [or anti-viral signaling protein (MAVS), virus-induced signaling adaptor (VISA) or CARD adaptor inducing IFN-[alpha] (Cardif)], and when it interacts with the CARD domain, allows the recruitment of dsRNA, which results in the expression of type-I IFN due to the activation and translocation of IRF3, IRF7 and NF-[kappa]B to the nucleus (32,33).
This model of action is consistent with the ability of NS1 expression to prevent activation of transcription factors involved in the induction of IFN[alpha]/[beta] synthesis, including IRF3 (16).
MAVS [52] is an essential component of the innate immune response pathway: dsRNA is recognized by RIG-I which leads via activation of IRF3 to the expression of IFN-beta.
The researchers discovered that the viral protein vpu, which is created by HIV during infection, directly interferes with the immune response protein IRF3 to dampen the ability of the immune system to protect against virus infection.
En la via independiente de MyD88, las moleculas TRIF y TRAM (molecula adaptadora relacionada con TRIF por la sigla en ingles de trif-related adaptor molecule)sirven de moleculas adaptadoras que reclutan y activan la cinasa TBK-1 (cinasa de union a TANK, activador de Nf-[kappa]B por las siglas en ingles de tank-binding kinase [TBK-1] y TRAF family member-associated Nf-[kappa]B activator [TANK]) para la posterior activacion de IRF3 (factor regulador de interferon -IFN- 3, por la sigla en ingles de interferon regulatory factor 3), el cual se desplaza al nucleo e induce la transcripcion de genes responsables de la produccion de IFN tipo I y de moleculas coestimuladoras.
A signaling molecule called IRF3, which is an essential component of innate immunity and is required for hepatocyte apoptosis, may play a unique role in the processes leading to hepatocyte apoptosis in ALD and tying together alcohol-induced liver inflammation, metabolic disturbances, and cell death (Petrasek et al.