Thread by @Kariem_Ezzat

Our new preprint showing that viruses such as HSV-1 & #SARSCoV2 can induce amyloid aggregation proteins in human CSF. Viruses act as nucleation catalysts for amyloid formation, which is driven by protein supersaturation, not conformational templating. 1/7
biorxiv.org/content/10.110…

This is why no prion/protein template was required to obtain these results & UV-inactivation didn’t affect the ability of the viruses to act as nucleation catalysts. While UV-inactivation destroys viral nucleic acids, it does not affect the ability of viruses to act as..2/7

..catalytic surfaces that induce amyloid aggregation via the mechanism of heterogeneous nucleation. The driver (supersaturation) & information (intermolecular backbone hydrogen bonding) for amyloid formation are in the recipient environment, and thus the process doesn’t..3/7

..require donor seeds or templating prions. Our results show that viruses should not be excluded from neurodegenerative etiology, neither based on the UV-inactivation argument nor based on the conformational templating argument. Viral catalytic activity survives..4/7

..UV-inactivation & no conformational templating is required to obtain the amyloid conformation (cross-β), which is a spontaneous folding event under supersaturated conditions. In fact, the ability of viruses to trigger amyloid aggregation taken together with their ability..5/7

..to invade the CNS (remain latent/reactivate) make them far more likely candidates for the induction of amyloid aggregation in the brain compared to prion infection (seeding), which has been mostly demonstrated via the artificial procedure of direct injection into the brain. 6/7

This is particularly important in understanding post-infection neurological sequelae such as #LongCOVID & how this mechanism contributes to the pathology.

Many thanks to all the coauthors including: @KlingstromLab @SandbergLabKI @LabMalm @AlbertoEspay @andrea_sturchio 7/7