Some studies report that Ripk3 −/− mice are more susceptible to IAV infection suggesting the importance of this protein in the in vivo protection against IAV infection 5, 7, 17. RIPK3 was reported to be crucial for the protection against IAV.
This results in RIPK3 autophosphorylation and phosphorylation of its substrate mixed lineage kinase domain-like pseudokinase (MLKL) 13, 14 which destabilizes the plasma membrane and executes necroptosis 15, 16. Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) is activated by RIP Homology Interaction Motif (RHIM)-dependent recruitment to RIPK1, TIR-domain-containing adapter-inducing interferon-β (TRIF) or Z-nucleic acid Binding Protein-1 (ZBP1) 10, 12. From an evolutionary point of view necroptosis is an alternative cell death mechanism that promotes the killing of host cells that acquired resistance to caspase-8-mediated cell-extrinsic apoptosis and can also restrict pathogen replication 11. These viral proteins allow viruses to escape PCD. Many viruses have evolved genes that can block apoptosis such as viral inhibitor of caspase-8 activation (vICA) and viral mitochondria-localized inhibitor of apoptosis (vMIA) in mouse cytomegalovirus (MCMV) 10. Apoptosis is the major type of PCD upon in vitro infection of cells with IAV 3, 4, but necroptosis and pyroptosis were also shown to be elicited 5– 9. Programmed cell death (PCD) plays a role as a cell-autonomous defense mechanism by which infected cells die resulting in limited viral replication and spreading 2. In mammals, IAV typically infects lung epithelial cells and replicates in the nucleus where the virus also hijacks the host’s transcription machinery 1. IAVs can cause influenza in birds and some mammals, including humans. Influenza A viruses (IAVs) are negative-stranded RNA viruses that belong to the Orthomyxoviridae family.
0 kommentar(er)
