Track 8: Viral Infection In Down Syndrome

Viral infections is less common in people with Down syndrome, but when they do occur, the sickness they cause is more severe. Increasing levels of an antiviral cytokine type I interferon (IFN-I), which is largely coded for by chromosome 21, are the source of this, according to recent research. Increased IFN-I levels trigger an initial overreaction of the immune system, but the body overcompensates to lower inflammation, leaving the body more vulnerable to viral infection later. While immunological dysfunction is evident in patients with Down syndrome, the exact mechanism by which a supernumerary chromosome 21 results in the dysregulation of defenses is yet unknown.

The virologists studied fibroblasts and white blood cells produced by people with and without Down syndrome at both the mRNA and protein levels to fill this information gap. They concentrated on the chromosome 21-based IFN-I receptor subunits IFNAR1 and IFNAR2, which are powerful antiviral cytokines. Independent of trisomy 21, the virologists discovered that elevated IFNAR2 expression was sufficient to cause the IFN-I hypersensitivity seen in Down syndrome. But afterward, the excessively powerful IFN-I signaling cascade activated a protein called USP18, a strong IFNAR negative regulator, to provide excessive negative feedback. Further IFN-I responses and antiviral responses were subsequently inhibited by this approach. Together, the data show that Down syndrome is predisposed to oscillations of hyper- and hypo-responses to IFN-I, which reduce the incidence of illness and raise infection-related morbidity and death.


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