Type I interferon activity was originally described over 50 years ago as a soluble factor produced by cells treated with inactivated, non-replicating viruses that blocked subsequent infection with live virus. Although the rapid induction and amplification of the type I interferon system is highly adaptive in terms of virus eradication, aberrant stimulation or unregulated control of the system could lead to inappropriate and / or excessive interferon output. Studies of the AGS-related proteins TREX1, the RNase H2 complex, SAMHD1 and ADAR1, suggest that an inappropriate accumulation of self-derived nucleic acids can induce type I interferon signaling. The findings of IFIH1 mutations in the similar context implicates the aberrant sensing of nucleic acids as a cause of immune upregulation. What is the source of the nucleic acid inducing the immune disturbance in AGS? Intriguingly, it has been shown that TREX1 can metabolise reverse-transcribed HIV-1 DNA and that single-stranded DNA derived from endogenous retroelements accumulates in Trex1-deficient cells; however, the upregulation of retroelements in TREX1-null cells has recently been disputed. Similarly, another AGS-related gene product SAMHD1 also presents strong potency against activity of multiple non-LTR retroelements, which is independent from SAMHD1's famous dNTPase activity.
Aicardi–Goutières syndrome
Witteveen–Kolk syndrome
Pork–cat syndrome
Woodhouse–Sakati syndrome
RAPADILINO syndrome
Phidippides cardiomyopathy
Bannayan–Riley–Ruvalcaba syndrome
Galloway Mowat syndrome