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 W HeV induces an oxidative stress and W HeV 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 W HeV 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. Significance Statement Nipah and Hendra viruses are severe pathogens infecting humans and livestock, classified among the 8 highest priorities for research by the WHO. The W protein, along with the V protein, is a virulence factor responsible for antiviral response inhibition and we demonstrate here that its fibrillation into amyloid-like fibrils occurs in the nucleus of transfected cells, with their formation being dependent of the redox state of the W cysteine residues. The sole transfection of W provokes the production of reactive oxygen species, creating a suitable environment for the fibrils to form. Finally, we show that W fibrils enhance the repression of the antiviral response, thus pointing to W fibrillation as a new promising antiviral target.