Introducing the brain: neurons viruses and inflammation (Introduction)

by David Turell , Tuesday, November 14, 2023, 17:56 (373 days ago) @ David Turell

How neuron activity incites inflammation:

https://www.science.org/doi/10.1126/sciimmunol.adg2979?utm_source=sfmc&utm_medium=e...

In summary, neurons are specialized cells where PRRs constantly sense “self” dsRNAs to "preemptively induce protective antiviral immunity, but maintaining RNA homeostasis is paramount to prevent pathological neuroinflammation."

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"Editor’s summary
The central nervous system relies on pattern recognition receptors (PRRs) to trigger innate immune responses against neurotropic viruses, but excessive PRR activation can also contribute to neurodegenerative diseases. Dorrity et al. found that human neurons express particularly high levels of long double-stranded RNAs (dsRNA) that activate PRRs, leading to constitutive production of type I interferon (IFN-I). The ELAV-like RNA-binding proteins HuB and HuC generated elongated 3’ untranslated regions (UTRs) that gave rise to neuronal dsRNA structures. Loss of HuB and HuC increased susceptibility to herpes simplex virus 1 and Zika virus infection in wild-type neurons but improved survival of neurons lacking ADAR1, the gene mutated in Aicardi-Goutières syndrome. Together, these results identify elongated 3’UTRs as a source of immunostimulatory dsRNA in neurons that couples antiviral responses with pathological inflammation."

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A full review:

https://mail.google.com/mail/u/0/#inbox/FMfcgzGwHfrfhGnmNHQnhnRSZwPzMXvc

"According to research published recently in Science Immunology, one of these extra defenses is the production of double-stranded RNA by neurons (in red above), which essentially puts the brain’s immune system on high alert. Unfortunately, this may also predispose neurons to damaging levels of inflammation when there isn’t a virus to battle.

"Many viral genomes are packaged as double-stranded RNA, as opposed to the double-stranded DNA of our genomes. So, the human immune system generally considers long double-stranded RNA strings to be a sign of a viral infection. But our cells also can produce the stuff, and researchers studying the brain discovered that neurons produce a ton of double-stranded RNA all the time—even when they’re healthy.

"This appears to prime them to battle against viruses. When researchers lowered neurons’ production of these molecules, the cells were more susceptible to viral infections. On the flip side, they survived for longer when not infected. “The findings show how this tricky balance between susceptibility to infection and inflammation in the brain works in both health and disease,” Lawrence Tabak, former acting director of the National Institutes of Health, writes in a blog post . “It also leads to the tantalizing suggestion that treatments targeting these various players or others in the same pathways may offer new ways of treating brain infections or neuroinflammatory conditions.” Such treatments might work by ramping up or down the production of double-stranded RNA, he writes."

Comment: mimicking a virus to fight virus is an interesting trick and sets up a situation on a knife edge of danger as an autoimmune attack. From a designer standpoint, it is a designed mechanism to thwart viruses, recognizing the dangers viruses offer.