Redox-dependent formation of a viral amyloid and functional impact

Abstract

The Hendra and Nipah viruses (HeV and NiV) are zoonotic biosafety level-4 pathogens within the Paramyxoviridae family. We previously showed that their W proteins form amyloid-like fibrils in vitro. Here, we demonstrate that W also forms fibrils in cellula and that cysteine residues are crucial in dictating the ability of W proteins to fibrillate. The cysteine oxidation state acts as a switch to generate either amorphous aggregates or flexible fibrils. Ectopic expression of WHeV induces an oxidative stress and WHeV fibrils were observed in the nuclei of different cell lines, with fibrillation being impaired by cysteine substitutions. Finally, nuclear fibrils are associated with an impairment of the NF-κB pathway in WHeV transfected cells. This work provides experimental evidence for the ability of Henipavirus W proteins to fibrillate in transfected cells and the first clues on their functional impact.