S6K1 and S6K2 are required for Ad-induced activation of IRF3.
Researchers at McMaster University have discovered a critical step in the immune system’s recognition of DNA viruses. It’s a key finding, they say, that could lead to vaccinations for herpes, the common cold or even cancer. A protein, previously known to be involved in metabolism, is critical for the detection of the viruses.
“We have identified an important step in the detection of DNA viruses by the immune system, and have shown that this is absolutely crucial in the response to a vaccine against these infections. If the key immune system component identified in these studies is not triggered, then vaccination fails” said Prof. Lichty.
Wan says this study could have further impact on a number of serious conditions and illnesses. “This represents a breakthrough in our fundamental understanding of how our immune system detects a viral infection. But it goes beyond that, as this component of our immune system is also involved in detection of cancer by our immune system and is central to the development of autoimmune diseases,” Wan said. “So this discovery potentially impacts anyone infected by a virus, receiving a vaccination, fighting cancer or experiencing autoimmunity.”
Hydrophobic motif in the S6K1 structures
Prior to this study, it was known that interferon regulatory factor-3 (IRF-3), a protein coding gene ie transcription factor , contributed to a first line of defense against viral infection by triggering antiviral activity. However the activation of IRF-3 following infection was not fully understood. The study found an interaction with the protein S6K1 and the signaling adaptor STING is a fundamental regulatory mechanism for IRF3 and, thus, helps trigger antiviral responses.
ie infection with DNA viruses induced interaction of metabolic checkpoint kinase mTOR downstream effector and kinase S6K1 and STING in a manner dependent on the DNA sensor cGAS. The kinase domain, but not the kinase function, of S6K1 was required for the S6K1-STING interaction and TBK1 critically promoted this process. The formation of a tripartite S6K1-STING-TBK1 complex was necessary for the activation of IRF3, and disruption of this signaling axis impaired the early-phase expression of IRF3 target genes and the induction of T cell responses and mucosal antiviral immunity.
“Now that we have identified this aspect of the immune system, we can work on developing methods to engage this pathway during vaccination against viruses or cancer,” said Lichty. http://www.eurekalert.org/pub_releases/2016-04/mu-t040116.php
http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.3433.html
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