Rift Valley fever virus coordinates the assembly of a programmable E3 ligase to promote viral replication

Viruses use various strategies to degrade host cell proteins, thereby promoting their replication and dissemination. Through a collaboration with the laboratory of Prof. Ke Peng (Wuhan Institute of Virology, China), the iWays team contributed here to reveal that the non-structural protein NSs of Rift Valley fever virus (RVFV) forms a filamentous and programmable degradation machinery to induce organized degradation of cellular proteins to promote viral infection. Among other things, cryo-electron microscopy analysis led to (i) the determination of the structure of NSs filaments reconstituted in vitro at high resolution (2.9 Å) and (ii) the identification of amino residues important for NSs fibrillation. This study shows that NSs associates with the cellular factor FBXO3 to form a filamentous E3 ligase which ubiquitinates the TFIIH complex via the NSs-P62 interaction to induce its degradation. This degradation results in strong inhibition of antiviral immunity, contributing to RVFV-induced pathogenesis. Read all about the results in the article published in Cell (October 2024)