Chaoran Yin

Loading metrics Open Access Peer-reviewed Research Article Citation: Amusan OT, Wang S, Yin C, Koehler HS, Li Y, Tenev T, et al. (2025) RIPK1 is required for ZBP1-driven necroptosis in human cells. PLoS Biol 23(2): e3002845. https://doi.org/10.1371/journal.pbio.3002845 Academic Editor: Feng Shao, National Institute of Biological Sciences, CHINA Received: August 29, 2024; Accepted: January 6, 2025; Published: February 21, 2025 Copyright: © 2025 Amusan et al.

Abstract Necroptosis initiated by the host sensor Z-NA Binding Protein-1 (ZBP1) is essential for host defense against a growing number of viruses, including Herpes Simplex Virus-1 (HSV-1). Studies with HSV-1 and other necroptogenic stimuli in murine settings have suggested that ZBP1 triggers necroptosis by directly complexing with the kinase RIPK3. Whether this is also the case in human cells, or whether additional co-factors are needed for ZBP1-mediated necroptosis, is unclear.

Highlights • Replicating influenza A virus (IAV) produces Z-RNAs • IAV Z-RNAs are sensed by host ZBP1 in the nucleus • ZBP1 activates MLKL in the nucleus, triggering nuclear envelope rupture • MLKL-induced nuclear rupture and necroptosis drive IAV disease severity Summary Influenza A virus (IAV) is a lytic RNA virus that triggers receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mediated pathways of apoptosis and mixed lineage kinase domain-like pseudokinase (MLKL)-dependent...