Human SUMOylation Pathway Is Critical for Influenza B Virus

Abstract

The identification and elucidation of host pathways for viral infection are critical for understanding the viral infection processes and novel therapeutics development. Here, for the first time, we discover that the human SUMOylation pathway is essential for the IBV viral life cycle. First, IBV viruses were completely inhibited by a novel SUMOylation specific inhibitor, STE025, discovered from our FRET-based high-throughput screening, and the inhibition was very potent, with IC50~ 0.1 µM in an IBV-induced cell death rescue assay; Second, we determined that the IBV M1 protein was SUMOylated, which was mediated by the SUMOylation E2 conjugation enzyme and the E3 ligase enzyme at very high affinities, of 0.20 µM and 0.22 µM, respectively; Third, the mutation of the IBV M1 SUMOylation site, K21R, completely abolished the viral particle generation, strongly suggesting the requirement of SUMOylation for the IBV life cycle. These results suggest that the blockage of the host human SUMOylation pathway is very effective for IBV inhibition. We therefore propose that the host SUMOylation pathway is a critical host factor for the IBV virus life cycle. The identification and inhibition of critical host factor(s) provide a novel strategy for future anti-viral therapeutics development, such as IBV and other viruses.

Dissecting Human and Influenza Virus Interaction with qFRET Technology

“…contribution of the CyPet at 530 nm is proportionate to its peak emission at 475 nm (FL DD ) when stimulated at 414 at 530 nm is proportionate to its emission at 530 nm given a 475 nm excitation (FL AA signal was measured from 400 to 600 nm. This research demonstrates that the human SUMOylation pathway is required for the IBV life cycle 14 . The SUMOylation pathway, a pathway required for the IBV life cycle, can impede IBV viral replication.…”